Obesity and vulnerability of the CNS

Bruce-Keller, Annadora J.; Keller, Jeffrey N.; Morrison, Christopher D.

doi:10.1016/j.bbadis.2008.10.004

Cited by 200Adipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and ObesityDementia and Cognitive Impairment Research

Obesity and vulnerability of the CNS

Open access

Bruce-Keller, Annadora J., Keller, Jeffrey N., Morrison, Christopher D.·2009·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI 10.1016/j.bbadis.2008.10.004PMC PMC2699212

Open this paper in CoChat — free account Open PDF

Abstract

The incidence of obesity is increasing worldwide, and is especially pronounced in developed western countries. While the consequences of obesity on metabolic and cardiovascular physiology are well established, epidemiological and experimental data are beginning to establish that the central nervous system (CNS) may also be detrimentally affected by obesity and obesity-induced metabolic dysfunction. In particular, data show that obesity in human populations is associated with cognitive decline and enhanced vulnerability to brain injury, while experimental studies in animal models confirm a profile of heightened vulnerability and decreased cognitive function. This review will describe findings from human and animal studies to summarize current understanding of how obesity affects the brain. Furthermore, studies aimed at identifying key elements of body-brain dialog will be discussed to assess how various metabolic and adipose-related signals could adversely affect the CNS. Overall, data suggest that obesity-induced alterations in metabolism may significantly synergize with age to impair brain function and accelerate age-related diseases of the nervous system. Thus, enhanced understanding of the effects of obesity and obesity-related metabolic dysfunction on the brain are especially critical as increasing numbers of obese individuals approach advanced age.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.bbadis.2008.10.004

Cites

124 of 124 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The obesity-induced toxic internal environment does not spare the brain.
“It is becoming clear that the obesity-induced toxic internal environment does not spare the brain ([24](#B24), [46](#B46), [48](#B48), [52](#B52), [59](#B59), [95](#B95), [121](#B121), [127](#B127), [177](#B177), [182](#B182), [198](#B198)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [24]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
‘Small Changes' to Diet and Physical Activity Behaviors for Weight Management
Hills, A. P., Byrne, N. M., Lindstrom, R. C., & Hill, J. O. (2013) · Obesity Facts · doi:10.1159/000345030 · Cited by 9,526 · see citing works
Oxidants, antioxidants, and the degenerative diseases of aging.
Ames, B. N., Shigenaga, M. K., & Hagen, T. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7915 · Cited by 5,958 · see citing works
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405 · cited 1× · see citing works
“signal to the brain that suppresses appetite and increases energy expenditure [102].”
Global prevalence of dementia: a Delphi consensus study
Ferri, C. P., Prince, M. J., Brayne, C., Brodaty, H., Fratiglioni, L., Ganguli, M., Hall, K. S., Hasegawa, K., Hendrie, H. C., Huang, Y., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67889-0 · Cited by 5,336 · see citing works
Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study.
Hubert, H. B., Feinleib, M., McNamara, P. M., & Castelli, W. P. (1983) · Circulation · doi:10.1161/01.cir.67.5.968 · Cited by 4,241 · see citing works
Translational Findings on Brain-Derived Neurotrophic Factor and Anxiety: Contributions from Basic Research to Clinical Practice
da Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,012 · see citing works
Obesity
Haslam, D. W., & James, W. P. T. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67483-1 · Cited by 3,757 · see citing works
Identification and expression cloning of a leptin receptor, OB-R.
Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90151-5 · Cited by 3,496 · see citing works
The Obesity Epidemic in the United States Gender, Age, Socioeconomic, Racial/Ethnic, and Geographic Characteristics: A Systematic Review and Meta-Regression Analysis
Wang, Y., & Beydoun, M. A. (2007) · Epidemiologic Reviews · doi:10.1093/epirev/mxm007 · Cited by 2,779 · see citing works
Adipose tissue, adipokines, and inflammation
Fantuzzi, G. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.02.023 · Cited by 2,606 · see citing works
The Global Epidemic of Obesity: An Overview
Caballero, B. H. (2007) · Epidemiologic Reviews · doi:10.1093/epirev/mxm012 · Cited by 1,251 · cited 1× · see citing works
“Indeed, the global extent of the obesity pandemic was formally recognized by the World Health Organization (WHO) in 1997, and worldwide obesity rates are increasing dramatically [1].”
High‐fat Diets: Modeling the Metabolic Disorders of Human Obesity in Rodents
Buettner, R., Schölmerich, J., & Bollheimer, L. C. (2007) · Obesity · doi:10.1038/oby.2007.608 · Cited by 1,241 · cited 2× · see citing works
“Studies in which specially formulated high fat or calorie diets were given to experimental animals revealed that such diets promote obesity, hyperglycemia, whole-body insulin resistance, and generalized metabolic syndrome function [41,46,47].”
Leptin enters the brain by a saturable system independent of insulin
Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B., & Maness, L. M. (1996) · Peptides · doi:10.1016/0196-9781(96)00025-3 · Cited by 1,222 · cited 1× · see citing works
“Leptin enters the brain via a saturable transport mechanism [103] and while it is known that leptin acts on hypothalamic centers to regulate feeding behavior, leptin receptors (OBR) are widely expressed in numerous extra-hypothalamic regions of the brain, including the hippocampus, cerebellum, amygdale, and brain stem…”
The worldwide obesity epidemic
James, P. T., Leach, R., Kalamara, E., & Shayeghi, M. (2001) · Obesity Research · doi:10.1038/oby.2001.123 · Cited by 1,201 · cited 1× · see citing works
“In light of the 1 billion overweight and 300million obese individuals worldwide [18], a better understanding of the degree to which, and the mechanisms by which, obesity affects the brain could not only result in significant advances in public health, but could also unmask the pathophysiologic processes that might und…”
Validity of body mass index compared with other body-composition screening indexes for the assessment of body fatness in children and adolescents
Mei, Z., Grummer‐Strawn, L. M., Pietrobelli, A., Goulding, A., Goran, M. I., & Dietz, W. H. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/75.6.978 · Cited by 986 · cited 1× · see citing works
“identified based on measurements of body mass index [3], but can be generally defined as the physiological condition in which excess body fat has accumulated to an extent that can negatively affect health.”
A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning
Molteni, R., Barnard, R. J., Ying, Z., Roberts, C. K., & Gómez‐Pinilla, F. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00123-9 · Cited by 918 · see citing works
Discrete Microdomains with High Concentration of cAMP in Stimulated Rat Neonatal Cardiac Myocytes
Zaccolo, M., & Pozzan, T. (2002) · Science · doi:10.1126/science.1069982 · Cited by 858 · see citing works
Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships.
Lee, Y., Hirose, H., Ohneda, M., Johnson, J. H., McGarry, J., & Unger, R. H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10878 · Cited by 832 · see citing works
Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues.
Fei, H., Okano, H. J., Li, C., Lee, G.-H., Zhao, C., Darnell, R., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.7001 · Cited by 766 · see citing works
Diet‐induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle‐aged rats
Stranahan, A., Norman, E., Lee, K., Cutler, R., Telljohann, R., Egan, J., & Mattson, M. P. (2008) · Hippocampus · doi:10.1002/hipo.20470 · Cited by 755 · cited 1× · see citing works
“Studies have also examined biochemical and histological indices of synaptic dysfunction and reported that obesity is associated with decreases in dendritic spine density [57] and in the expression of synaptic marker proteins such as synapsin and GAP-43 [59–61].”
Adipokines: The missing link between insulin resistance and obesity
Antuna-Puente, B., Fève, B., Fellahi, S., & Bastard, J. (2008) · Diabetes & Metabolism · doi:10.1016/j.diabet.2007.09.004 · Cited by 738 · cited 1× · see citing works
“obesity, insulin resistance and related inflammatory disorders [99,100].”
Defining high-fat-diet rat models: Metabolic and molecular effects of different fat types
Buettner, R., Parhofer, K. G., Woenckhaus, M., Wrede, C. E., Kunz-Schughart, L. A., Schölmerich, J., & Bollheimer, L. C. (2006) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01909 · Cited by 704 · see citing works
Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study
Elias, M. F., Elias, P. K., SULLIVAN, L. M., Wolf, P. A., & D’Agostino, R. B. (2003) · International Journal of Obesity · doi:10.1038/sj.ijo.802225 · Cited by 691 · see citing works
Elevated body mass index is associated with executive dysfunction in otherwise healthy adults
Gunstad, J., Paul, R. H., Cohen, R. A., Tate, D. F., Spitznagel, M. B., & Gordon, E. (2007) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2006.05.001 · Cited by 668 · cited 1× · see citing works
“Other studies of young and middle-aged healthy adults have confirmed the association of obesity with behavioral declines in executive function [34].”
Weight and blood pressure. Findings in hypertension screening of 1 million Americans
Stamler, R. (1978) · JAMA · doi:10.1001/jama.240.15.1607 · Cited by 656 · see citing works
A Prospective Study of Body Mass Index, Weight Change, and Risk of Stroke in Women
Rexrode, K. M. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540430051032 · Cited by 617 · see citing works
Diabetic neuropathy—a review
Saïd, G. (2007) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0504 · Cited by 615 · cited 1× · see citing works
“[50,51], this study reported that genetically obese (ob/ob) mice had decreased overall levels of myelin andmarked alterations to the fatty acid”
Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons
Stranahan, A. M., Arumugam, T. V., Cutler, R. G., Lee, K. M., Egan, J. M., & Mattson, M. P. (2008) · Nature Neuroscience · doi:10.1038/nn2055 · Cited by 610 · see citing works
Regulation of lifespan by sensory perception in Caenorhabditis elegans
Apfeld, J., & Kenyon, C. (1999) · Nature · doi:10.1038/45544 · Cited by 573 · cited 1× · see citing works
“For example, studies in both Drosophila melanogaster and Caenorhabditis elegans have shown that genetic mutations that cause defects in sensory cilia or their support cells, or in sensory signal transduction, significantly extend lifespan [116,117].”
Synapsins as mediators of BDNF-enhanced neurotransmitter release
Jovanovic, J. N., Czernik, A. J., Fienberg, A. A., Greengard, P., & Sihra, T. S. (2000) · Nature Neuroscience · doi:10.1038/73888 · Cited by 566 · cited 1× · see citing works
“that BDNF supports synaptic plasticity and neuronal excitability [62], and appears to be important for maintaining learning and memory function, particularly in aging [63–65], these studies again support the hypothesis that obesity is able to accelerate the physiological indices of brain aging.”
The Magnitude of Dementia Occurrence in the World
Wimo, A. B., Winblad, B. G., Agüero‐Torres, H., & Strauss, E. I. V. (2003) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200304000-00002 · Cited by 536 · see citing works
Free Fatty Acids Produce Insulin Resistance and Activate the Proinflammatory Nuclear Factor-κB Pathway in Rat Liver
Boden, G., She, P., Mozzoli, M., Cheung, P., Gumireddy, K., Reddy, P., Xiang, X., Luo, Z., & Ruderman, N. (2005) · Diabetes · doi:10.2337/diabetes.54.12.3458 · Cited by 528 · see citing works
Body mass index and the risk of stroke in men
Kurth, T., Gaziano, J. M., Berger, K., Kase, C. S., Rexrode, K. M., Cook, N. R., Buring, J. E., & Manson, J. E. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.22.2557 · Cited by 524 · cited 2× · see citing works
“These studies are also important in that they indicate that the increased risk for stroke in overweight or obese subjects is independent of diabetes, hypertension, or hypercholesterolemia [27].”
Brain abnormalities in human obesity: A voxel-based morphometric study
Pannacciulli, N., Del Parigi, A., Chen, K., Le, D. S. N. T., Reiman, E. M., & Tataranni, P. A. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.01.047 · Cited by 523 · see citing works
Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier
Banks, W. A., Coon, A. B., Robinson, S. M., Moinuddin, A., Shultz, J. M., Nakaoke, R., & Morley, J. E. (2004) · Diabetes · doi:10.2337/diabetes.53.5.1253 · Cited by 512 · cited 1× · see citing works
“Finally, triglycerides have been shown to impair leptin transport through the blood–brain barrier [85], indicating that thewell-characterized phenomena of leptin resistance may be related in part to the action of triglycerides at the blood–brain barrier.”
Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl- l -carnitine and/or R -α-lipoic acid
Liu, J., Head, E., Gharib, A., Yuan, W., Ingersoll, R. T., Hagen, T. M., Cotman, C. W., & Ames, B. N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261709299 · Cited by 504 · cited 1× · see citing works
“Although the physiologic mechanisms whereby obesity adversely affects the brain are not understood (see Section 4, below), both experimental and human studies have shown that obesity is associated with increased oxidative stress, which has been implicated in cognitive declines seen in neurodegenerative diseases [70,71…”
Caloric Intake and the Risk of Alzheimer Disease
Luchsinger, J. A., Tang, M., Shea, S. A., & Mayeux, R. P. (2002) · Archives of Neurology · doi:10.1001/archneur.59.8.1258 · Cited by 470 · cited 1× · see citing works
“For example, retrospective studies have found that an elevation in BMI of only a single unit associates with a 36% increase in Alzheimer's disease in women [36], while a prospective study of a large cohort of people in New York City revealed that those with low-calorie or lowfat diets had significantly lower risks for…”
Postsynaptic induction of BDNF-mediated long-term potentiation
Kovalchuk, Y., Hanse, E., Kafitz, K. W., & Konnerth, A. (2002) · Science · doi:10.1126/science.1067766 · Cited by 456 · see citing works
The epidemiology of the dementias: an update
Qiu, C., Ronchi, D. D., & Fratiglioni, L. (2007) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e32816ebc7b · Cited by 418 · cited 1× · see citing works
“Overall, current evidence suggests that obesity and the consequences of obesity, including midlife hypertension, diabetes, and cerebrovascular disease, contribute significantly to cognitive decline and accelerate the development of dementia [35].”
Weight and Blood Pressure
Stamler, R. (1978) · JAMA · doi:10.1001/jama.1978.03290150053024 · Cited by 417 · see citing works
Mechanisms of Liver and Muscle Insulin Resistance Induced by Chronic High-Fat Feeding
Oakes, N. D., Cooney, G. J., Camilleri, S., Chisholm, D. J., & Kraegen, E. W. (1997) · Diabetes · doi:10.2337/diab.46.11.1768 · Cited by 414 · cited 1× · see citing works
“Studies in which specially formulated high fat or calorie diets were given to experimental animals revealed that such diets promote obesity, hyperglycemia, whole-body insulin resistance, and generalized metabolic syndrome function [41,46,47].”
Epidemiology of Dementia and Alzheimer's Disease
Hendrie, H. C. (1998) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-199821001-00002 · Cited by 410 · see citing works
Regulation of Drosophila Life Span by Olfaction and Food-Derived Odors
Libert, S., Zwiener, J., Chu, X., VanVoorhies, W., Roman, G., & Pletcher, S. D. (2007) · Science · doi:10.1126/science.1136610 · Cited by 410 · cited 3× · see citing works
“For example, studies in both Drosophila melanogaster and Caenorhabditis elegans have shown that genetic mutations that cause defects in sensory cilia or their support cells, or in sensory signal transduction, significantly extend lifespan [116,117].”
The interplay between oxidative stress and brain‐derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition
Wu, A., Ying, Z., & Gómez‐Pinilla, F. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03246.x · Cited by 402 · cited 1× · see citing works
“AMP-response element-binding protein (CREB), and prevents obesity-induced alterations to cognitive function [61].”
Obesity, diabetes and cognitive deficit: The Framingham Heart Study
Elias, M. F., Elias, P. K., Sullivan, L. M., Wolf, P. A., & D’Agostino, R. B. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.08.019 · Cited by 395 · see citing works
Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results.
Sparks, D. L., Sabbagh, M. N., Connor, D. J., Lopez, J., Launer, L. J., Browne, P. J., Wasser, D., Johnson‐Traver, S., Lochhead, J. J., & Ziolwolski, C. (2005) · PubMed · doi:10.1001/archneur.62.5.753 · Cited by 394 · cited 1× · see citing works
“Positive studies related to the role of cholesterol in dementia have primarily related to effects of statin drug use, but these studies have also yielded mixed results, with a generally diminished risk for dementia although some of the tests did not achieve statistical significance [82].”
Regulation of C. elegans Longevity by Specific Gustatory and Olfactory Neurons
Alcedo, J., & Kenyon, C. (2004) · Neuron · doi:10.1016/s0896-6273(03)00816-x · Cited by 388 · see citing works
Obesity and Hypertriglyceridemia Produce Cognitive Impairment
Farr, S. A., Yamada, K. A., Butterfield, D. A., Abdul, H. M., Xu, L., Miller, N. E., Banks, W. A., & Morley, J. E. (2008) · Endocrinology · doi:10.1210/en.2007-1722 · Cited by 382 · cited 1× · see citing works
“For example, it has been shown that direct administration of triglycerides can impair hippocampal longterm potentiation, and that lowering of triglycerides pharmacologically with gemfibrozil reduces the expressionofmarkers of oxidative stress in the brains of obese mice [83].”
The Physiology of Obese-Hyperglycemic Mice [ob/obMice]
Lindström, P. (2007) · The Scientific World JOURNAL · doi:10.1100/tsw.2007.117 · Cited by 353 · cited 1× · see citing works
“In addition to obesity and hyperphagia, mutant mice exhibit transient diabetes-like syndrome of hyperglycemia, glucose intolerance, elevated plasma insulin, and impaired wound healing (reviewed in [43]).”
The effect of body mass index on global brain volume in middle-aged adults: a cross sectional study
Ward, M. A., Carlsson, C. M., Trivedi, M. A., Sager, M. A., & Johnson, S. C. (2005) · BMC Neurology · doi:10.1186/1471-2377-5-23 · Cited by 346 · cited 1× · see citing works
“For example, regression studies in which the effects of age and body mass index (BMI) on brain volume and cognitionweremeasured demonstrated that both age and increased BMI were associated with decreased brain volume [19].”
Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease
Cao, D., Lu, H., Lewis, T. L., & Li, L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703561200 · Cited by 336 · cited 1× · see citing works
“For instance, obesity-induced by a high calorie diet has been shown to increase insoluble amyloid burden and decrease cognitive performance in a transgenic mouse model of Alzheimer's disease [66].”
High-fat diets, insulin resistance and declining cognitive function
Greenwood, C. E., & Winocur, G. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.08.017 · Cited by 330 · see citing works
Obesity‐related leptin regulates Alzheimer's Aβ
Fewlass, D. C., Noboa, K., Pi‐Sunyer, F. X., Johnston, J. M., Yan, S. D., & Tezapsidis, N. (2004) · The FASEB Journal · doi:10.1096/fj.04-2572com · Cited by 308 · see citing works
Body Size and Fat Distribution as Predictors of Stroke among US Men
Walker, S. P., Rimm, E. B., Ascherio, A., Kawachi, I. I., Stampfer, M. J., & Willett, W. C. (1996) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a008892 · Cited by 296 · see citing works
Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms
Mattson, M. P., Duan, W., & Guo, Z. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01586.x · Cited by 288 · cited 1× · see citing works
“indeed has been suggested to be altered by diet [72].”
Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats
Oomura, Y., Hori, N., Shiraishi, T., Fukunaga, K., Takeda, H., Tsuji, M., Matsumiya, T., Ishibashi, M., Aou, S., Li, X. L., et al. (2006) · Peptides · doi:10.1016/j.peptides.2006.07.001 · Cited by 284 · cited 1× · see citing works
“For example, it has been shown that direct administration of leptin into the dentate gyrus enhances long-term potentiation [110], and that intravenous administration of leptin to rats facilitates behavioral performance in passive avoidance and Morris water-maze tasks [111].”
High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex
ZHANG, X., Dong, F., Ren, J. T., Driscoll, M., & Culver, B. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.10.011 · Cited by 280 · cited 1× · see citing works
“calorie diets to rodents increases free radical generation [73] and protein oxidation [74] in the brain.”
Obesity Is an Independent Risk Factor of Mortality in Severely Injured Blunt Trauma Patients
Neville, A. L. (2004) · Archives of Surgery · doi:10.1001/archsurg.139.9.983 · Cited by 272 · cited 1× · see citing works
“Indeed, while some studies have shown that obesity is an independent predictor of mortality following blunt trauma [24], other studies have failed to detect increases in mortality following traumatic injury in obese patients, although it was noted”
Change in Cognitive Function by Glucose Tolerance Status in Older Adults: A 4-Year Prospective Study of the Rancho Bernardo Study Cohort
Kanaya, A. M., Barrett-Connor, E., Gildengorin, G., & Yaffe, K. (2004) · Archives of Internal Medicine · doi:10.1001/archinte.164.12.1327 · Cited by 255 · cited 1× · see citing works
“For example, retrospective studies have found that an elevation in BMI of only a single unit associates with a 36% increase in Alzheimer's disease in women [36], while a prospective study of a large cohort of people in New York City revealed that those with low-calorie or lowfat diets had significantly lower risks for…”
Studies of the effects of high fat diets on cognitive function in a rat model
Winocur, G., & Greenwood, C. E. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.003 · Cited by 243 · cited 1× · see citing works
“would be altered synaptic transmission, and indeed, animal studies have confirmed that experimental obesity is associated with a wide array of cognitive abnormalities [55,56].”
Overview of Adipose Tissue and Its Role in Obesity and Metabolic Disorders
Frühbeck, G. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-245-8_1 · Cited by 226 · see citing works
A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor
Wu, A., Molteni, R., Ying, Z., & Gómez‐Pinilla, F. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00154-4 · Cited by 223 · cited 1× · see citing works
“Other studies have likewise shown that diet-induced obesity is able to synergize with traumatic brain injury in decreasing hippocampal plasticity and learning [60].”
Prolonged Reactive Oxygen Species Generation and Nuclear Factor-κB Activation after a High-Fat, High-Carbohydrate Meal in the Obese
Patel, C., Ghanim, H., Ravishankar, S. T., Sia, C. L., Viswanathan, P., Mohanty, P., & Dandona, P. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0778 · Cited by 221 · see citing works
Rodent obesity models: An overview
Tschöp, M. H., & Heiman, M. L. (2001) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2001-17297 · Cited by 220 · cited 2× · see citing works
“mechanical intervention (chemical lesion of the ventromedial hypothalamus), and use of these animal models has contributed strongly to the understanding of human obesity (reviewed in [41,42]).”
Metabolic Syndrome and Cognitive Decline in Elderly Latinos: Findings from the Sacramento Area Latino Study of Aging Study
Yaffe, K. S., Haan, M. N., BLACKWELL, T. L., Cherkasova, E., Whitmer, R. A., & West, N. A. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01139.x · Cited by 210 · see citing works
Interactive relations of central versus total obesity and blood pressure to cognitive function
Waldstein, S. R., & Katzel, L. I. (2005) · International Journal of Obesity · doi:10.1038/sj.ijo.0803114 · Cited by 200 · see citing works
Glucocorticoids, chronic stress, and obesity
Dallman, M. F., Pecoraro, N. C., La Fleur, S. E., Warne, J. P., Ginsberg, A. B., Akana, S. F., Laugero, K. C., Houshyar, H., Strack, A. M., Bhatnagar, S., et al. (2006) · Progress in Brain Research · doi:10.1016/s0079-6123(06)53004-3 · Cited by 198 · see citing works
Expression of BDNF and trkB as a function of age and cognitive performance
Croll, S. D., Ip, N. Y., Lindsay, R. M., & Wiegand, S. J. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00993-7 · Cited by 197 · see citing works
Body mass index and magnetic resonance markers of brain integrity in adults
Gazdzinski, S., Kornak, J., Weiner, M. W., & Meyerhoff, D. J. (2008) · Annals of Neurology · doi:10.1002/ana.21377 · Cited by 191 · cited 1× · see citing works
“matter and myelin abnormalities in association with obesity [53,54].”
Orexin-A (Hypocretin-1) and leptin enhance LTP in the dentate gyrus of rats in vivo
Wayner, M. J., Armstrong, D. L., Phelix, C. F., & Oomura, Y. (2004) · Peptides · doi:10.1016/j.peptides.2004.03.018 · Cited by 190 · cited 1× · see citing works
“For example, it has been shown that direct administration of leptin into the dentate gyrus enhances long-term potentiation [110], and that intravenous administration of leptin to rats facilitates behavioral performance in passive avoidance and Morris water-maze tasks [111].”
Overweight and Obese Humans Demonstrate Increased Vascular Endothelial NAD(P)H Oxidase-p47 phox Expression and Evidence of Endothelial Oxidative Stress
Silver, A., Beske, S. D., Christou, D. D., Donato, A. J., Moreau, K. L., Eskurza, I., Gates, P. E., & Seals, D. R. (2007) · Circulation · doi:10.1161/circulationaha.106.657486 · Cited by 190 · see citing works
Vascular Lipotoxicity: Endothelial Dysfunction via Fatty-Acid-Induced Reactive Oxygen Species Overproduction in Obese Zucker Diabetic Fatty Rats
Chinen, I., Shimabukuro, M., Yamakawa, K., Higa, N., Matsuzaki, T., Noguchi, K., Ueda, S., Sakanashi, M., & Takasu, N. (2006) · Endocrinology · doi:10.1210/en.2006-1132 · Cited by 187 · cited 1× · see citing works
“overactivation of NADPH oxidase, which in turn is caused by circulating free fatty acids [75].”
Can Dementia Be Prevented? Brain Aging in a Population-Based Context
Haan, M. N., & Wallace, R. B. (2004) · Annual Review of Public Health · doi:10.1146/annurev.publhealth.25.101802.122951 · Cited by 187 · cited 1× · see citing works
“syndrome, and cardiovascular disease [17].”
Leptin regulation of neuronal excitability and cognitive function
Harvey, J. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.10.006 · Cited by 184 · cited 1× · see citing works
“While the full extant of leptin's actions on the brain have not been characterized, the past decade of research has not only revealed that leptin receptors are widely expressed in the CNS, but has also identified numerous additional functions for this hormone in the brain [107].”
Risk factors for myocardial infarction in Brazil
Piegas, L. S., Avezum, Á., Pereira, J. C. R., Neto, J. M. R., Hoepfner, C., Farran, J. A., Ramos, R. F., Timerman, A., & Esteves, J. P. (2003) · American Heart Journal · doi:10.1016/s0002-8703(03)00181-9 · Cited by 180 · cited 1× · see citing works
“myocardial infarction [8], and stroke [9,10], one could theorize that obesity accelerates age and age-related pathologies.”
Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like behavior
de Souza, C. G., Moreira, J. D., Siqueira, I. R., Pereira, A. G., Rieger, D. K., Souza, D. O., Souza, T. M. E., Portela, L. V., & Perry, M. L. S. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.05.001 · Cited by 168 · cited 1× · see citing works
“calorie diets to rodents increases free radical generation [73] and protein oxidation [74] in the brain.”
The Spectrum of Diabetic Neuropathies
Tracy, J. A., & Dyck, P. J. B. (2008) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2007.10.010 · Cited by 164 · see citing works
Plasma HDL Levels Highly Correlate With Cognitive Function in Exceptional Longevity
Atzmon, G., Gabriely, I., Greiner, W., Davidson, D., Schechter, C. B., & Barzilai, N. (2002) · The Journals of Gerontology Series A · doi:10.1093/gerona/57.11.m712 · Cited by 164 · see citing works
Leptin: a potential cognitive enhancer?
Harvey, J., Shanley, L. J., O'Malley, D., & Irving, A. J. (2005) · Biochemical Society Transactions · doi:10.1042/bst0331029 · Cited by 162 · see citing works
Leptin-Induced IL-6 Production Is Mediated by Leptin Receptor, Insulin Receptor Substrate-1, Phosphatidylinositol 3-Kinase, Akt, NF-κB, and p300 Pathway in Microglia
Tang, C., Lu, D.-Y., Yang, R., Tsai, H.-Y., Kao, M., Fu, W., & Chen, Y. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.2.1292 · Cited by 160 · see citing works
Diet-induced obesity and spatial cognition in young male rats
Jurdak, N. A., Lichtenstein, A. H., & Kanarek, R. B. (2008) · Nutritional Neuroscience · doi:10.1179/147683008x301333 · Cited by 153 · see citing works
Prevalence of dementia according to DSM–III–R and ICD–10
Riedel-Heller, S. G., Busse, A., Aurich, C., Matschinger, H., & Angermeyer, M. C. (2001) · The British Journal of Psychiatry · doi:10.1192/bjp.179.3.250 · Cited by 149 · see citing works
Prevalence of dementia subtypes: A 30-year retrospective survey of neuropathological reports
Brunnström, H., Gustafson, L., Passant, U., & Englund, E. M. (2008) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2008.06.005 · Cited by 148 · see citing works
Brain White Matter Expansion in Human Obesity and the Recovering Effect of Dieting
Haltia, L. T., Viljanen, A., Parkkola, R., Kemppainen, N., Rinne, J. O., Nuutila, P., & Kaasinen, V. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2495 · Cited by 139 · cited 1× · see citing works
“differ significantly in obese and lean subjects, andwere not affected by dieting [21].”
Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons
Patil, S. P., & Chan, C. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.05.003 · Cited by 138 · cited 1× · see citing works
“cultured macrophages [90,91], and also to modulate astrocytic and microglial signaling [92].”
Adipokines in Obesity
Ahima, R. S., & Osei, S. Y. (2008) · Frontiers of hormone research · doi:10.1159/000115365 · Cited by 136 · see citing works
The Response of the Aged Brain to Stroke: Too Much, Too Soon?
Popa‐Wagner, A., Carmichael, S. T., Kokaia, Z., Kessler, C., & Walker, L. C. (2007) · Current Neurovascular Research · doi:10.2174/156720207781387213 · Cited by 134 · cited 1× · see citing works
“In relation to other forms of injury, advanced age is a major risk factor for stroke, and has been reported to increase the severity of stroke-induced brain dysfunction [26].”
Impact of plasma lipids and time on memory performance in healthy elderly without dementia
Reitz, C., Luchsinger, J. A., Tang, M. ‐., Manly, J. J., & Mayeux, R. P. (2005) · Neurology · doi:10.1212/01.wnl.0000158274.31318.3c · Cited by 126 · see citing works
Clinical and laboratory diagnosis of the metabolic syndrome
Olufadi, R., & Byrne, C. D. (2008) · Journal of Clinical Pathology · doi:10.1136/jcp.2007.048363 · Cited by 123 · cited 1× · see citing works
“and proinflammatory markers (reviewed in [5]).”
Interactive Effect of Obesity Indexes on Cognition
Jeong, S., Nam, H., Son, M.-H., Son, E.-J., & Cho, K.-H. (2004) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000082659 · Cited by 113 · see citing works
Inflammatory and Injury Responses to Ischemic Stroke in Obese Mice
Terao, S., Yılmaz, G., Stokes, K. Y., Ishikawa, M., Kawase, T., & Granger, D. N. (2008) · Stroke · doi:10.1161/strokeaha.107.494542 · Cited by 112 · cited 2× · see citing works
“In relation to stroke, studies have shown that blood–brain barrier dysfunction and infarct volume following middle cerebral artery occlusion is increased in genetically obese mice compared to non-obese wild type mice [45].”
Relevance of animal models to human eating disorders and obesity
Casper, R. C., Sullivan, E. L., & Tecott, L. H. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1102-2 · Cited by 107 · cited 1× · see citing works
“mechanical intervention (chemical lesion of the ventromedial hypothalamus), and use of these animal models has contributed strongly to the understanding of human obesity (reviewed in [41,42]).”
Body mass index and thromboembolic stroke in nonsmoking men in older middle age. The Honolulu Heart Program.
Abbott, R. D., Behrens, G. R., Sharp, D. S., Rodríguez, B. L., Burchfiel, C. M., Ross, G. W., Yano, K., & Curb, J. D. (1994) · Stroke · doi:10.1161/01.str.25.12.2370 · Cited by 104 · see citing works
Cognitive dysfunction associated with metabolic syndrome
Taylor, V. H., & MacQUEEN, G. M. (2007) · Obesity Reviews · doi:10.1111/j.1467-789x.2007.00401.x · Cited by 102 · see citing works
Palmitic acid induces IP-10 expression in human macrophages via NF-κB activation
Laine, P. S., Schwartz, E. A., Wang, Y., Zhang, W.-Y., Karnik, S. K., Musi, N., & Reaven, P. D. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.04.092 · Cited by 99 · cited 2× · see citing works
“cultured macrophages [90,91], and also to modulate astrocytic and microglial signaling [92].”
Enhanced susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in high-fat diet-induced obesity
Choi, J., Jang, E.-H., Park, C., & Kang, J. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.12.008 · Cited by 98 · cited 1× · see citing works
“Finally, it has also been established that neurodegeneration induced by specific neurotoxins is increased by both genetic [68] and diet-induced obesity [69].”
Leptin induces interleukin‐1β release from rat microglial cells through a caspase 1 independent mechanism
Pinteaux, E., Inoue, W., Schmidt, L., Molina-Holgado, F., Rothwell, N., & Luheshi, G. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04559.x · Cited by 96 · cited 1× · see citing works
“Finally, leptin has been shown to modulate the inflammatory signaling in microglia [112,113] which could affect brain inflammatory and oxidative pathways.”
The Clinical Pharmacokinetics of Quinapril
Olson, S. C., Horvath, A. M., Michniewicz, B. M., Sedman, A. J., Colburn, W. A., Welling, P. G., & Olson, S. C. (1989) · Angiology · doi:10.1177/000331978904000404 · Cited by 93 · see citing works
Expression of free fatty acid receptor GPR40 in the neurogenic niche of adult monkey hippocampus
Ma, D., Lu, L., Boneva, N. B., Warashina, S., Kaplamadzhiev, D. B., Mori, Y., Nakaya, M., Kikuchi, M., Tonchev, A. B., Okano, H., et al. (2007) · Hippocampus · doi:10.1002/hipo.20393 · Cited by 93 · cited 1× · see citing works
“hippocampus [89], and the saturated free fatty acids palmitic acid and lauric acid have both been shown to cause inflammatory signaling in”
The Metabolic Syndrome and Aging
Morley, J. E. (2004) · The Journals of Gerontology Series A · doi:10.1093/gerona/59.2.m139 · Cited by 92 · cited 1× · see citing works
“While postulated indirect mechanisms include the effects of hyperglycemia on brain energetics and/or vascular damage to the central nervous system [78], it is well known that consumption of a high fat diet and/ or increased adiposity causes dramatic changes in the profile of bioactive serum lipids, including cholester…”
Obesity and Traumatic Brain Injury
Brown, C., Rhee, P., Neville, A. L., Sangthong, B., Salim, A., & Δημητριάδης, Δ. (2006) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/01.ta.0000200842.19740.38 · Cited by 85 · see citing works
Various Dietary Fats Differentially Change the Gene Expression of Neuropeptides Involved in Body Weight Regulation in Rats
Dziedzic, B., Szemraj, J., Bartkowiak, J., & Walczewska, A. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01541.x · Cited by 81 · see citing works
Brain myelin of genetically obese mice
Sena, A., Sarliève, L. L., & Rebel, G. (1985) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(85)90104-2 · Cited by 79 · cited 1× · see citing works
“compositionof themyelin as compared towild typemice [52].”
Obesity exacerbates chemically induced neurodegeneration
Sriram, K., Benkovic, S. A., Miller, D. B., & O’Callaghan, J. P. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00306-8 · Cited by 78 · see citing works
Older age, traumatic brain injury, and cognitive slowing: Some convergent and divergent findings.
Bashore, T. R., & Ridderinkhof, K. R. (2002) · Psychological Bulletin · doi:10.1037/0033-2909.128.1.151 · Cited by 76 · see citing works
Metabolic syndrome in patients with acute myocardial infarction is associated with increased infarct size and in-hospital complications
Clavijo, L., Pinto, T. L., Kuchulakanti, P. K., Torguson, R., Chu, W. W., Satler, L. F., Kent, K. M., Suddath, W. O., Pichard, A. D., & Waksman, R. (2006) · Cardiovascular revascularization medicine · doi:10.1016/j.carrev.2005.10.007 · Cited by 75 · see citing works
Triglyceride levels affect cognitive function in noninsulin-dependent diabetics
Perlmuter, L. C., Nathan, D. M., Goldfinger, S. H., Russo, P. A., Yates, J., & Larkin, M. E. (1988) · Journal of Diabetes and its Complications · doi:10.1016/s0891-6632(88)80011-4 · Cited by 74 · cited 1× · see citing works
“These studies are further supported by clinical studies inwhich it has beenshown thatelevated triglycerides are associated with poor cognitive performance in patients with type 2 diabetes [84], and by studies in which the reduction of hypertriglyceridemia with gemfibrozil improved cerebral blood flow and function on t…”
Obesity and Outcomes After Blunt Trauma
Duane, T. S. M., Dechert, T. A., Aboutanos, M. B., Malhotra, A. K., & Ivatury, R. R. (2006) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/01.ta.0000241022.43088.e1 · Cited by 60 · cited 1× · see citing works
“that obese individuals had longer hospital stays compared to nonobese patients [25].”
The Multiple Facets of the Fat Tissue
Rocha, V. Z., & Libby, P. (2008) · Thyroid · doi:10.1089/thy.2007.0296 · Cited by 59 · see citing works
Modulation of Longevity by Environmental Sensing
Libert, S., & Pletcher, S. D. (2007) · Cell · doi:10.1016/j.cell.2007.12.002 · Cited by 56 · cited 1× · see citing works
“As a final note, there is a body of data that suggests a potential scenario whereby the sensory perception (generally via olfaction or taste) of calories or nutrients might significantly influence the activity of metabolic hormones and modulate lifespan [114,115].”
Reducing Hypertriglyceridemia in Elderly Patients with Cerebrovascular Disease Stabilizes or Improves Cognition and Cerebral Perfusion
Rogers, R. L., Meyer, J. S., McClintic, K., & Mortel, K. F. (1989) · Angiology · doi:10.1177/0003319789040004043 · Cited by 56 · cited 1× · see citing works
“These studies are further supported by clinical studies inwhich it has beenshown thatelevated triglycerides are associated with poor cognitive performance in patients with type 2 diabetes [84], and by studies in which the reduction of hypertriglyceridemia with gemfibrozil improved cerebral blood flow and function on t…”
Life span: getting the signal from the nervous system
Wolkow, C. A. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02133-1 · Cited by 52 · cited 1× · see citing works
“As a final note, there is a body of data that suggests a potential scenario whereby the sensory perception (generally via olfaction or taste) of calories or nutrients might significantly influence the activity of metabolic hormones and modulate lifespan [114,115].”
Accelerated cognitive aging in diabetic rats is prevented by lowering corticosterone levels
Stranahan, A. M., Lee, K. M., Pistell, P. J., Nelson, C. M., Readal, N., Miller, M. G., Spangler, E. L., Ingram, D. K., & Mattson, M. P. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2008.05.005 · Cited by 48 · see citing works
Taste-Induced Changes in Plasma Insulin and Glucose Turnover in Lean and Genetically Obese Rats
Ionescu, E., Rohner-Jeanrenaud, F., Proietto, J., Rivest, R., & Jeanrenaud, B. (1988) · Diabetes · doi:10.2337/diab.37.6.773 · Cited by 46 · cited 1× · see citing works
“induce cephalic-phase insulin release, and to increase hepatic glucose production in rats [119].”
What Can Imaging Reveal about Obesity and the Brain?
Jagust, W. J. (2007) · Current Alzheimer Research · doi:10.2174/156720507780362146 · Cited by 43 · cited 1× · see citing works
“matter and myelin abnormalities in association with obesity [53,54].”
Hypothalamic Neuronal Histamine in Genetically Obese Animals: Its Implication of Leptin Action in the Brain
Itateyama, E., Chiba, S., Sakata, T., & Yoshimatsu, H. (2003) · Experimental Biology and Medicine · doi:10.1177/153537020322801006 · Cited by 33 · cited 1× · see citing works
“to measure the effects of obesity on the brain [44,45].”
Lipotoxic effects of triacylglycerols in J774.2 macrophages
Aronis, A., Madar, Z., & Tirosh, O. (2008) · Nutrition · doi:10.1016/j.nut.2007.10.017 · Cited by 32 · see citing works
Anticonvulsant effects of leptin in epilepsy
Diano, S., & Horváth, T. L. (2007) · Journal of Clinical Investigation · doi:10.1172/jci34511 · Cited by 32 · cited 1× · see citing works
“In particular, there is evidence that leptin influences neuronal excitability via the activation and trafficking of potassium channels in several brain regions, which may be important in regulation of food intake, cognition, and also anti-convulsant effects [108].”
Incidence of Dementia According to DSM–III–R and ICD–10
Riedel-Heller, S. G., Busse, A., Aurich, C., Matschinger, H., & Angermeyer, M. C. (2001) · The British Journal of Psychiatry · doi:10.1192/bjp.179.3.255 · Cited by 30 · see citing works
Targeting the Liver in the Metabolic Syndrome: Evidence from Animal Models
Petruzzelli, M., Sasso, G. L., Portincasa, P., Palasciano, G., & Moschetta, A. (2007) · Current Pharmaceutical Design · doi:10.2174/138161207781039625 · Cited by 21 · see citing works
[Long-term prognosis of cerebral infarct in comparison with a normal population].
Weitbrecht, W.-U., & Kirchhoff, D. (1995) · PubMed · Cited by 5 · see citing works
Conclusions and Unanswered Questions
Rolfe, R. D., & Finegold, S. M. (1988) · Elsevier eBooks · doi:10.1016/b978-0-12-593410-7.50024-7 · Cited by 3 · see citing works
Untitled work
Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4

Flagged first, then by citations

Research works printed but not linked: 1

[65]Kovalchuk Y Hanse E Kafitz KW Konnerth A Postsynaptic induction of BDNF-mediated long-term potentiation Science 295 2002 1729 1734 11872844

Sorted by citations

Reward, dopamine and the control of food intake: implications for obesity
Volkow, N. D., Wang, G.-J., & Baler, R. D. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2010.11.001 · Cited by 1,400 · see citing works
“There is increasing evidence that obesity is associated with impairment on certain cognitive functions, such as executive function, attention and memory [73–75].”
Brain fuel metabolism, aging, and Alzheimer’s disease
Cunnane, S. C., Nugent, S., Roy, M., Courchesne‐Loyer, A., Croteau, É., Tremblay, S., Castellano, A., Pifferi, F., Bocti, C., Paquet, N., et al. (2010) · Nutrition · doi:10.1016/j.nut.2010.07.021 · Cited by 607 · see citing works
“Obesity predisposes younger adults to the metabolic syndrome, which appears to increase the risk of degenerative changes in the brain [92].”
Background
Cognitive impairment following high fat diet consumption is associated with brain inflammation
Pistell, P. J., Morrison, C. D., Gupta, S., Knight, A. G., Keller, J. N., Ingram, D. K., & Bruce‐Keller, A. J. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.11.010 · Cited by 594 · see citing works
“Overall, these data are consistent with a growing body of literature describing the sensitivity of the brain to obesity and obesityinduced metabolic dysfunction (reviewed in Bruce-Keller et al., 2009).”
Self-citation
Obesity-Induced Neuroinflammation: Beyond the Hypothalamus
Guillemot‐Legris, O., & Muccioli, G. G. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.02.005 · Cited by 565 · see citing works
Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity
Bruce-Keller, A. J., Salbaum, J. M., Luo, M., Blanchard, E., Taylor, C. M., Welsh, D. A., & Berthoud, H.-R. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.07.012 · Cited by 563 · see citing works
“of mental illness is obesity, which dramatically increases risk of depression, dementia, and stroke, and is associated with increased brain pathology and decreased brain function [reviewed in (2)].”
Self-citation
Integration of cellular bioenergetics with mitochondrial quality control and autophagy
Hill, B. G., Benavides, G. A., Lancaster, J. R., Ballinger, S. W., Dell’Italia, L., Zhang, J., & Darley-Usmar, V. M. (2012) · Biological Chemistry · doi:10.1515/hsz-2012-0198 · Cited by 481 · see citing works
Neuroimaging and obesity: current knowledge and future directions
Carnell, S., Gibson, C., Benson, L., Ochner, C. N., & Geliebter, A. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2011.00927.x · Cited by 441 · see citing works
“Biological mediators could include the physiological effects of sleep apnoea (33), increased adipose tissue hormone secretions such as leptin (34), or release of pro-inflammatory factors caused by consuming high-fat diets (35).”
Saturated long‐chain fatty acids activate inflammatory signaling in astrocytes
Gupta, S., Knight, A. G., Gupta, S., Keller, J. N., & Bruce‐Keller, A. J. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07660.x · Cited by 339 · see citing works
Self-citation
High fat diet increases hippocampal oxidative stress and cognitive impairment in aged mice: implications for decreased Nrf2 signaling
Morrison, C. D., Pistell, P. J., Ingram, D. K., Johnson, W. D., Liu, Y., Fernandez‐Kim, S. O., White, C. L., Purpera, M. N., Uranga, R. M., Bruce‐Keller, A. J., et al. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06865.x · Cited by 291 · see citing works
Self-citation
Why is obesity such a problem in the 21st century? The intersection of palatable food, cues and reward pathways, stress, and cognition
Morris, M. J., Beilharz, J. E., Maniam, J., Reichelt, A. C., & Westbrook, R. F. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.12.002 · Cited by 285 · see citing works
Food reward, hyperphagia, and obesity
Berthoud, H.-R., Lenard, N. R., & Shin, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00028.2011 · Cited by 275 · see citing works
“It is becoming clear that the obesity-induced toxic internal environment does not spare the brain (24, 46, 48, 52, 59, 95, 121, 127, 177, 182, 198).”
Background
Neuroinflammation and neurodegeneration in overnutrition-induced diseases
Cai, D. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.11.003 · Cited by 256 · see citing works
Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: Contributions of maternal diet
White, C. L., Pistell, P. J., Purpera, M. N., Gupta, S., Fernandez-Kim, S.-O., Hise, T. L., Keller, J. N., Ingram, D. K., Morrison, C. D., & Bruce-Keller, A. J. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.04.002 · Cited by 245 · see citing works
“Indeed, epidemiological and experimental data have established that the brain is sensitive to obesity and obesity-induced metabolic dysfunction (reviewed in Bruce-Keller et al., 2008).”
Self-citation
Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation
André, C., Dinel, A.-L., Ferreira, G., Layé, S., & Castanon, N. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.03.012 · Cited by 241 · see citing works
Short exposure to a diet rich in both fat and sugar or sugar alone impairs place, but not object recognition memory in rats
Beilharz, J. E., Maniam, J., & Morris, M. J. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.11.016 · Cited by 234 · see citing works
“Excessive intake of this diet leads to increased body weight, progression into obesity, and the development of metabolic and cardiovascular disorders (Bruce-Keller et al., 2009; Haslam and James, 2005).”
Background
Maternal pre‐pregnancy obesity and risk for inattention and negative emotionality in children
Rodriguez, A. (2009) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2009.02133.x · Cited by 233 · see citing works
Obesity associated with increased brain age from midlife
Ronan, L., Alexander‐Bloch, A. F., Wagstyl, K., Farooqi, I. S., Brayne, C., TYLER, L. K., & Fletcher, P. C. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.010 · Cited by 228 · see citing works
“Although the exact biological mechanisms are complex (Arnoldussen et al., 2014; Bruce-Keller et al., 2009; Cai, 2013; Chung et al., 2009),1 suggestion is that proinflammatory cytokines (such as interleukin 6 and tumor necrosis factor-a) and associated hormones such as leptin, produced by adipose tissue, elicit an infl…”
Background
Ghrelin signalling and obesity: At the interface of stress, mood and food reward
Schellekens, H., Finger, B. C., Dinan, T. G., & Cryan, J. F. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.06.004 · Cited by 229 · see citing works
“Contents lists available at SciVerse ScienceDirect Pharmacology & Therapeutics j ou rna l homepage: www.e lsev ie r .com/ locate /pharmthera Associate editor: P. Holzer Ghrelin signalling and obesity: At the interface of stress, mood and food reward Harriët Schellekens a,e, Beate C. Finger a,e, Timothy G. Dinan a,b,c,…”
BackgroundInfluential
Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions
Beilharz, J. E., Maniam, J., & Morris, M. J. (2015) · Nutrients · doi:10.3390/nu7085307 · Cited by 214 · see citing works
“These topics have been reviewed in detail elsewhere [8,9].”
Background
Secret talk between adipose tissue and central nervous system via secreted factors—an emerging frontier in the neurodegenerative research
Parimisetty, A., Dorsemans, A.-C., Awada, R., Ravanan, P., Diotel, N., & d’Hellencourt, C. L. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0530-x · Cited by 208 · see citing works
“Indeed, over the last decade, a number of magnetic resonance imaging (MRI) and computed tomography (CT) studies also reported alterations in brain morphology of overweight/obese individuals [40–42].”
Background
Structural Brain Changes Associated with Overweight and Obesity
Apo, E. G., Mondragón‐Maya, A., Ferrari-Díaz, M., & Silva‐Pereyra, J. (2021) · Journal of Obesity · doi:10.1155/2021/6613385 · Cited by 203 · see citing works
“Other studies have shown that obesity in healthy mature adults is associated with axonal and/or myelin abnormalities in the white matter and decreased gray matter volumes that can reflect neuronal loss [119].”
Background
The effects of a high-energy diet on hippocampal-dependent discrimination performance and blood–brain barrier integrity differ for diet-induced obese and diet-resistant rats
Davidson, T. L., Monnot, A. D., Neal, A. U., Martin, A., Horton, J., & Zheng, W. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.05.015 · Cited by 202 · see citing works
“The present results add to a number of epidemiological and experimental studies which suggest that common mechanisms may link obesity and metabolic disease to the emergence of cognitive dysfunction [24-26].”
Result
Obesity Reduces Cognitive and Motor Functions across the Lifespan
Wang, C., Chan, J. S. Y., Ren, L., & Yan, J. H. (2016) · Neural Plasticity · doi:10.1155/2016/2473081 · Cited by 199 · see citing works
“Some also suggest that obesityrelated changes in metabolism interact with age to impair brain functions [72].”
Background
Intentional weight loss in overweight and obese individuals and cognitive function: a systematic review and meta‐analysis
Siervo, M., Arnold, R. J., Wells, J. C. K., Tagliabue, A., Colantuoni, A., Albanese, E., Brayne, C., & Stephan, B. C. M. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2011.00903.x · Cited by 198 · see citing works
“The mechanisms by which obesity influences brain structure are unknown but may be linked to increased vascular and metabolic insult mediated by increased oxidative stress or inflammation (64).”
Background
Obesity: Pathophysiology and Intervention
Zhang, Y., Liu, J., Yao, J., Ji, G., Qian, L., Wang, J., Zhang, G., Tian, J., Nie, Y., Zhang, Y., et al. (2014) · Nutrients · doi:10.3390/nu6115153 · Cited by 191 · see citing works
“Sleep apnea [123], increased secretion of adipocyte hormones such as leptin [124], or release of proinflammatory factors due to high-fat consumption may be physiological factors mediating the changes”
Background
Harnessing Gut Microbes for Mental Health: Getting From Here to There
Bruce‐Keller, A. J., Salbaum, J. M., & Berthoud, H. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.08.014 · Cited by 188 · see citing works
“Mental illness contributes substantially to the global burden of disability, and to uncover new avenues for treatment the generally tight association of neurobehavioral and metabolic dysfunction has come under intense scrutiny (15),(16),(17).”
BackgroundSelf-citation
Childhood Obesity, Cortical Structure, and Executive Function in Healthy Children
Ronan, L., Alexander‐Bloch, A. F., & Fletcher, P. C. (2019) · Cerebral Cortex · doi:10.1093/cercor/bhz257 · Cited by 190 · see citing works
“For example, in adult populations, a significant number of studies have suggested that obesity may play a causal role in the onset of brain structural changes and cognitive decline (Bruce-Keller et al. 2009; Arnoldussen et al. 2014).”
Background
Gut Microbiota: The Brain Peacekeeper
Mu, C., Yang, Y., & Zhu, W. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00345 · Cited by 188 · see citing works
Obesity and Aging
Bischof, G. N., & Park, D. C. (2015) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000212 · Cited by 182 · see citing works
“However, some hypotheses that have been proposed are as follows: a) hyperglycemia (higher blood glucose levels) is associated with a high-fat diet and has been shown to damage the vascular system and may indirectly affect brain shrinkage through decreases in neurons or impaired neurogenesis (55); b) recent evidence su…”
Background
Short-term exposure to a diet high in fat and sugar, or liquid sugar, selectively impairs hippocampal-dependent memory, with differential impacts on inflammation
Beilharz, J. E., Maniam, J., & Morris, M. J. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.03.018 · Cited by 169 · see citing works
Neuroanatomical differences in obesity: meta-analytic findings and their validation in an independent dataset
García‐García, I., Michaud, A., Dadar, M., Zeighami, Y., Neseliler, S., Collins, D. L., Evans, A. C., & Dagher, A. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0164-4 · Cited by 167 · see citing works
Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus
Soczynska, J. K., Kennedy, S. H., Woldeyohannes, H. O., Liauw, S. S. L., Alsuwaidan, M. T., Yim, C. Y., & McIntyre, R. S. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-010-8140-8 · Cited by 162 · see citing works
“Deficits in learning, memory, and executive function are reported in obese when compared to lean individuals (Bruce-Keller et al. 2009).”
Neurodegeneration in an animal model of Parkinson’s disease is exacerbated by a high-fat diet
Morris, J. K., Bomhoff, G. L., Stanford, J. A., & Geiger, P. C. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00449.2010 · Cited by 163 · see citing works
High-fat diet consumption disrupts memory and primes elevations in hippocampal IL-1β, an effect that can be prevented with dietary reversal or IL-1 receptor antagonism
Sobesky, J. L., Barrientos, R. M., May, H. S. D., Thompson, B. M., Weber, M. D., Watkins, L. R., & Maier, S. F. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.06.017 · Cited by 160 · see citing works
“This notion is supported by observations that waist circumference in humans is linked to augmented physiological stress responses (Brydon, 2011) and that obesity induces increased vulnerability of the CNS to the negative impacts of stress and injury (Yehuda et al., 2005; Bruce-Keller et al., 2009).”
Regional astrogliosis in the mouse hypothalamus in response to obesity
Buckman, L. B., Thompson, M. M., Moreno, H. N., & Ellacott, K. L. J. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23233 · Cited by 148 · see citing works
“…Online Library (wileyonlinelibrary.com) 1322 The Journal of Comparative Neurology | Research in Systems Neuroscience 521:1322–1333 (2013) (CNS) (Bruce-Keller et al., 2009); for example, obese individuals have a 6% higher incidence of stroke for every unit increase in body mass index greater…”
BackgroundInfluential
Momordica charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation
Nerurkar, P. V., Johns, L. M., Buesa, L. M., Kipyakwai, G. K., Volper, E. M., Sato, R., Shah, P. A., Fehér, D., Williams, P. G., & Nerurkar, V. R. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-64 · Cited by 145 · see citing works
“Background The rising epidemic of obesity is associated not only with diabetes and cardiovascular diseases, but also brain dysfunction and early onset of dementia [1].”
Background
Body mass index correlates negatively with white matter integrity in the fornix and corpus callosum: A diffusion tensor imaging study
Xu, J., Yang, L., Lin, H., Sinha, R., & Potenza, M. N. (2011) · Human Brain Mapping · doi:10.1002/hbm.21491 · Cited by 138 · see citing works
“diets and increased blood levels of free fatty acids, leptin, and other chemicals associated with energy metabolism [Bruce-Keller et al., 2009; Cazettes et al., 2011; Pistell et al., 2010].”
Background
Caloric Restriction in Older Adults—Differential Effects of Weight Loss and Reduced Weight on Brain Structure and Function
Prehn, K., von Schwartzenberg, R. J., Mai, K., Zeitz, U., Witte, A. V., Hampel, D. J., Szela, A.-M., Fabian, S., Grittner, U., Spranger, J., et al. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw008 · Cited by 135 · see citing works
Maternal Prepregnancy BMI and Child Cognition: A Longitudinal Cohort Study
Basatemür, E., GARDINER, J. S., Williams, C. L., Melhuish, E. C., Barnes, J., & Sutcliffe, A. G. (2012) · PEDIATRICS · doi:10.1542/peds.2012-0788 · Cited by 125 · see citing works
Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice
Kaczmarczyk, M. M., Machaj, A. S., Chiu, G. S., Lawson, M. A., Gainey, S. J., York, J. M., Meling, D. D., Martin, S. A., Kwakwa, K. A., Newman, A. F., et al. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.01.004 · Cited by 123 · see citing works
“In humans, obesity impacts a variety of biobehaviors especially mood and cognition (Elias et al., 2003; Elias, et al., 2005; Bruce-Keller et al., 2009; Cserjesi et al., 2009) but how obesity impairs these brain-based functions remains unclear.”
Insulin Sensitivity as a Mediator of the Relationship Between BMI and Working Memory‐Related Brain Activation
Gonzales, M. M., Tarumi, T., Miles, S. C., Tanaka, H., Shah, F., & Haley, A. P. (2010) · Obesity · doi:10.1038/oby.2010.183 · Cited by 121 · see citing works
“including vascular damage, inflammation, triglycerides, and circulating levels of glucocorticoids (8).”
Background
The Obese Brain: Mechanisms of Systemic and Local Inflammation, and Interventions to Reverse the Cognitive Deficit
Salas-Venegas, V., Flores-Torres, R. P., Rodríguez-Cortés, Y. M., Rodríguez-Retana, D., Carreto, R. J. R., Concepción-Carrillo, L. E., Pérez-Flores, L. J., Alarcón‐Aguilar, A., López‐Díazguerrero, N. E., Gómez‐González, B., et al. (2022) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2022.798995 · Cited by 118 · see citing works
The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder
Yim, C. Y., Soczynska, J. K., Kennedy, S. H., Woldeyohannes, H. O., Brietzke, E. M., & McIntyre, R. S. (2011) · European Psychiatry · doi:10.1016/j.eurpsy.2011.02.004 · Cited by 110 · see citing works
“It is well established that impairments in executive function are apparent in mixed populations of individuals with BD as well as obese individuals without psychiatric disorders [7,10,16,19, 22,26,27,28,41,45].”
Background
Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer’s Disease
Vinuesa, Á., Pomilio, C. J., Gregosa, A., Bentivegna, M., Presa, J., Bellotto, M., Saravia, F., & Beauquis, J. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.653651 · Cited by 111 · see citing works
“In the last decade, the gut microbiome has gained increasing interest due to its role in the physiology of humans and several animal models including rodents (Bruce-Keller et al., 2009).”
Background
Dietary Factors in the Etiology of Parkinson’s Disease
Ağım, Z. S., & Cannon, J. R. (2015) · BioMed Research International · doi:10.1155/2015/672838 · Cited by 107 · see citing works
“HFD increases nigral dopaminergic neurons susceptibility to environmental insults [125].”
Background
Dietary inflammatory index and memory function: population-based national sample of elderly Americans
Frith, E., Shivappa, N., Mann, J. R., Hébert, J. R., Wirth, M. D., & Loprinzi, P. D. (2018) · British Journal Of Nutrition · doi:10.1017/s0007114517003804 · Cited by 105 · see citing works
“For example, chronic obesity may detrimentally influence memory function through morphological brain changes, insulin resistance, neuroinflammation, TAG metabolism, circulating levels of glucocorticoids and cerebral metabolite concentrations((9)).”
Background
High Fat Diet Exacerbates Neuroinflammation in an Animal Model of Multiple Sclerosis by Activation of the Renin Angiotensin System
Timmermans, S., Bogie, J. F. J., Vanmierlo, T., Lütjohann, D., Stinissen, P., Hellings, N., & Hendriks, J. J. A. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9502-4 · Cited by 104 · see citing works
“In addition, obese mice show a decreased amount of myelin and marked changes in the composition of myelin, indicating that myelination in the CNS is affected by dietary compounds (Sena et al. 1985; Bruce-Keller et al. 2009; Winer et al. 2009).”
An Akkermansia muciniphila subtype alleviates high-fat diet-induced metabolic disorders and inhibits the neurodegenerative process in mice
Wu, F., Guo, X., Zhang, M., Ou, Z., Wu, D., Deng, L., Lü, Z., Zhang, J., Deng, G., Chen, S., et al. (2019) · Anaerobe · doi:10.1016/j.anaerobe.2019.102138 · Cited by 100 · see citing works
Oxidative Stress and Altered Mitochondrial Function in Neurodegenerative Diseases: Lessons From Mouse Models
Fernández-Checa, J. C., Fernandez, A., Morales, A., Marı́, M., García‐Ruiz, C., & Colell, A. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791556113 · Cited by 98 · see citing works
“Clearly, uncontrolled generation of ROS would be expected to affect different cells and hence the course of progression of multiple pathologies linked to neurodegeneration, such as obesity, insulin sensitivity, cardiovascular and liver diseases, which have been covered in recent reviews [11-13].”
Background
NOX2 deficiency attenuates markers of adiposopathy and brain injury induced by high-fat diet
Pepping, J. K., Freeman, L. R., Gupta, S., Keller, J. N., & Bruce‐Keller, A. J. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00398.2012 · Cited by 94 · see citing works
Self-citation
Lipids and Cognition
Morley, J. E., & Banks, W. A. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-091576 · Cited by 108 · see citing works
“The metabolic alterations associated with obesity interact with aging to reduce cognition and accelerate the onset of age-related dementia processes [102].”
The Socioeconomic Burden of Obesity
Kjellberg, J., Larsen, A. T., Ibsen, R., & Højgaard, B. (2017) · Obesity Facts · doi:10.1159/000480404 · Cited by 86 · see citing works
The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice
Moon, M. L., Joesting, J. J., Lawson, M. A., Chiu, G. S., Blevins, N. A., Kwakwa, K. A., & Freund, G. G. (2014) · Metabolism · doi:10.1016/j.metabol.2014.06.002 · Cited by 82 · see citing works
“While longstanding overnutrition is linked to alterations in brain function and neuropsychiatric complications [8, 51], short-term overnutrition, in both rodents and humans, can generate adverse biobehaviors.”
Background
Re-thinking the Etiological Framework of Neurodegeneration
Castillo, X., Castro‐Obregón, S., Gutiérrez-Becker, B., Gutiérrez‐Ospina, G., Karalis, N., Khalil, A. A., López‐Noguerola, J. S., Rodríguez, L. L., Martínez‐Martínez, E., Perez‐Cruz, C., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00728 · Cited by 80 · see citing works
“In particular, data show that obesity is associated with cognitive decline and enhanced vulnerability to brain injury, while experimental studies in animal models confirm a profile of increased susceptibility to brain damage and decreased cognitive function (Bruce-Keller et al., 2009).”
Background
Relationship Between Obesity, Alzheimer’s Disease, and Parkinson’s Disease: an Astrocentric View
Martín-Jiménez, C., Gaitán-Vaca, D. M., Echeverrı́a, V., González, J., & Barreto, G. E. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0193-8 · Cited by 77 · see citing works
Stress-Induced Cytokines and Neuronal Dysfunction in Alzheimer's Disease
Ricci, S., Fuso, A., Ippoliti, F., & Businaro, R. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110821 · Cited by 76 · see citing works
“Overall, the above-reported data are consistent with a growing body of literature describing the sensitivity of the brain to obesity and obesity-induced metabolic dysfunction [123].”
Brain structure and cognitive correlates of body mass index in healthy older adults
Bolzenius, J. D., Laidlaw, D. H., Cabeen, R. P., Conturo, T. E., McMichael, A. R., Lane, E., Heaps, J. M., Salminen, L. E., Baker, L. M., Scott, S. E., et al. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.10.010 · Cited by 74 · see citing works
Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma
Johnson, L. A., Zuloaga, K. L., Kugelman, T., Mader, K. S., Morré, J. T., Zuloaga, D. G., Weber, S. J., Marzulla, T., Mulford, A., Button, D. A., et al. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.12.008 · Cited by 73 · see citing works
“While the precise biologicalmechanisms bywhich obesity andweight loss affect cognitive function are unclear, several plausible pathways exist, including oxidative stress, inflammation,metabolic impairments and vascular dysfunction (Bruce-Keller et al., 2009).”
Background
Histone Deacetylase Inhibitor, Trichostatin A, Improves Learning and Memory in High-Fat Diet-Induced Cognitive Deficits in Mice
Sharma, S., Taliyan, R., & Ramagiri, S. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0461-x · Cited by 74 · see citing works
“Both aging and HFD consumption have been reported to cause increased brain oxidative damage (Bruce-Keller et al. 2009; Zhang et al. 2009).”
Background
Mechanisms of Granulin Deficiency: Lessons from Cellular and Animal Models
Kleinberger, G., Capell, A., Haass, C., & Broeckhoven, C. V. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8380-8 · Cited by 72 · see citing works
“A link between neurodegenerative diseases and obesity has been suggested and a number of studies associate obesity with cognitive decline and enhanced vulnerability to brain injury [137].”
Background
The microbiota-gut-brain axis in hippocampus-dependent learning and memory: current state and future challenges
Kuijer, E. J., & Steenbergen, L. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105296 · Cited by 71 · see citing works
Mitochondrial Abnormalities and Synaptic Loss Underlie Memory Deficits Seen in Mouse Models of Obesity and Alzheimer’s Disease
Martins, I. V. A., Rivers‐Auty, J., Allan, S. M., & Lawrence, C. B. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160640 · Cited by 70 · see citing works
“Keywords: 3xTgAD, Alzheimer’s disease, high-fat diet, memory, mitochondria, Non-Tg, obesity, synapses”
NOX activity in brain aging: Exacerbation by high fat diet
Bruce‐Keller, A. J., White, C. L., Gupta, S., Knight, A. G., Pistell, P. J., Ingram, D. K., Morrison, C. D., & Keller, J. N. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.03.006 · Cited by 67 · see citing works
“Indeed, VHFD mice were heavier than WD mice at each age, and increased obesity per se could potentially mediate neurological perturbations noted in this study, as epidemiological and experimental data have established that the brain is sensitive to obesity and obesity-induced metabolic dysfunction (reviewed in [49]).”
BackgroundSelf-citation
Neuroinflammatory and autonomic mechanisms in diabetes and hypertension
Han, C., Rice, M. W., & Cai, D. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00012.2016 · Cited by 63 · see citing works
Evidences of a new psychobiotic formulation on body composition and anxiety
Colica, C., Avolio, E., Bollero, P., Costa de Miranda, R., Ferraro, S., Sinibaldi Salimei, P., De Lorenzo, A., & Di Renzo, L. (2017) · Mediators of Inflammation · doi:10.1155/2017/5650627 · Cited by 63 · see citing works
“At the same time, anxiety and other psychological disorders seem to be related to body composition and obesity [31].”
Background
Obesity and episodic memory function
Loprinzi, P. D., & Frith, E. (2018) · The Journal of Physiological Sciences · doi:10.1007/s12576-018-0612-x · Cited by 63 · see citing works
A randomised controlled trial of manualized cognitive remediation therapy in adult obesity
Raman, J., Hay, P., Tchanturia, K., & Smith, E. (2017) · Appetite · doi:10.1016/j.appet.2017.12.023 · Cited by 61 · see citing works
“…executive function, with obesity impacting on executive functioning via biological mechanisms and impaired executive functioning increasing the risk of obesity v a disordered eating patterns and behaviours (Elias et al., 2003; Bruce-Keller et al., 2009; Smith et al., 2011; Stanek & Gunstad, 2013).”
Background
Unravelling the impacts of western-style diets on brain, gut microbiota and cognition
Kendig, M. D., Leigh, S., & Morris, M. J. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.05.031 · Cited by 60 · see citing works
Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity
Tomlinson, L., Leiton, C. V., & Colognato, H. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.09.016 · Cited by 59 · see citing works
“…in saturated fats have a deleterious impact on white matter integrity, cognitive function, neuronal plasticity, neurotrophic signaling and activation of the stress-related hypothalamicpituitary-adrenal axis (Auvinen et al., 2012; Bruce-Keller et al., 2009; Freeman et al., 2014; White et al., 2009).”
Background
High-Fat Diet Induces Toll-Like Receptor 4-Dependent Macrophage/Microglial Cell Activation and Retinal Impairment
Lee, J., Wang, P., Yang, I.-H., Huang, H., Chang, C., Wu, C., & Chuang, J. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-16504 · Cited by 55 · see citing works
Adult obese mice suffer from chronic secondary brain injury after mild TBI
Sherman, M., Liu, M., Birnbaum, S. G., Wolf, S. E., Minei, J. P., & Gatson, J. W. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0641-4 · Cited by 53 · see citing works
“In the brain, links between obesity, neuroinflammation, neurodegeneration, deficits in neurogenesis, and cognitive/mood disorders have been reported [10–25].”
Background
The Impact of Obesity and Exercise on Cognitive Aging
Chan, J. S. Y., Yan, J. H., & Payne, V. G. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00097 · Cited by 52 · see citing works
“Triglyceride adversely affects the neural system after its breakdown into free fatty acids (Bruce-Keller et al., 2009).”
Background
Grape Seed and Skin Extract Prevents High-Fat Diet-Induced Brain Lipotoxicity in Rat
Charradi, K., Elkahoui, S., Karkouch, I., Limam, F., Hassine, F. B., & Aouani, E. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0821-2 · Cited by 51 · see citing works
Meningeal and choroid plexus cells—Novel drug targets for CNS disorders
Dragunow, M. (2013) · Brain Research · doi:10.1016/j.brainres.2013.01.013 · Cited by 50 · see citing works
Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice
Kim, T.-W., Choi, H.-H., & Chung, Y.-R. (2016) · Journal of Exercise Rehabilitation · doi:10.12965/jer.1632644.322 · Cited by 50 · see citing works
“Obesity impaired cognitive function and increased vulnerability to brain damage (Bruce-Keller et al., 2009).”
Background
Sodium butyrate ameliorates neurotoxicity and exerts anti-inflammatory effects in high fat diet-fed mice
Bayazid, A. B., Kim, J. G., Azam, S., Jeong, S. A., Kim, D. H., Park, C. W., & Lim, B. O. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112743 · Cited by 49 · see citing works
Physical exercise promotes memory capability by enhancing hippocampal mitochondrial functions and inhibiting apoptosis in obesity-induced insulin resistance by high fat diet
Park, H.-S., Cho, H.-S., & Kim, T.-W. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-0160-8 · Cited by 47 · see citing works
Metabolic and neurologic consequences of chronic lopinavir/ritonavir administration to C57BL/6 mice
Pistell, P. J., Gupta, S., Knight, A. G., Domingue, M., Uranga, R. M., Ingram, D. K., Kheterpal, I., Ruiz, C., Keller, J. N., & Bruce‐Keller, A. J. (2010) · Antiviral Research · doi:10.1016/j.antiviral.2010.10.006 · Cited by 43 · see citing works
“These data are consistent with a new but growing body of literature describing the sensitivity of the brain to metabolic dysfunction (reviewed in (Bruce-Keller et al., 2009).”
Self-citation
A comparative study about EPA-PL and EPA-EE on ameliorating behavioral deficits in MPTP-induced mice with Parkinson’s disease by suppressing oxidative stress and apoptosis
Wang, C., Wang, D., Zhang, T., Yanagita, T., Xue, C., Chang, Y., & Wang, Y. (2018) · Journal of Functional Foods · doi:10.1016/j.jff.2018.09.027 · Cited by 42 · see citing works
Doenjang, A Korean Traditional Fermented Soybean Paste, Ameliorates Neuroinflammation and Neurodegeneration in Mice Fed a High-Fat Diet
Ko, J. W., Chung, Y.-S., Kwak, C. S., & Kwon, Y. H. (2019) · Nutrients · doi:10.3390/nu11081702 · Cited by 40 · see citing works
“Oxidative stress could lead to increased inflammatory cytokine levels, memory loss, and neuronal apoptosis [26,27].”
Background
Food quality and motivation: A refined low-fat diet induces obesity and impairs performance on a progressive ratio schedule of instrumental lever pressing in rats
Blaisdell, A. P., Lau, Y. L. M., Telminova, E., Lim, H. C., Fan, B., Fast, C. D., Garlick, D., & Pendergrass, D. C. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.02.025 · Cited by 39 · see citing works
“Although the effects of HFD feeding on cognition have been explored [11 – 15], little is known about the impact of re ﬁ ned vs. unre ﬁ ned food on cognition, and it remains dif ﬁ cult to disentangle the effects of dietary fat from the effects of HFD-induced obesity.”
Glutaredoxin 2 (GRX2) deficiency exacerbates high fat diet (HFD)-induced insulin resistance, inflammation and mitochondrial dysfunction in brain injury: A mechanism involving GSK-3β
Wo-hua, Z., & Weiming, X. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108940 · Cited by 39 · see citing works
Gut and Brain: Investigating Physiological and Pathological Interactions Between Microbiota and Brain to Gain New Therapeutic Avenues for Brain Diseases
Deidda, G., & Biazzo, M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.753915 · Cited by 36 · see citing works
Obesity and Bipolar Disorder: Synergistic Neurotoxic Effects?
Liu, C. S., Carvalho, A. F., Mansur, R. B., & McIntyre, R. S. (2013) · Advances in Therapy · doi:10.1007/s12325-013-0067-7 · Cited by 36 · see citing works
Aerobic Interval Training Regulated SIRT3 Attenuates High-Fat-Diet-Associated Cognitive Dysfunction
Shi, Z., Li, C., Yin, Y., Yang, Z., Han, X. M., Mu, N., Wang, Y., Liu, M., & Ma, H. (2018) · BioMed Research International · doi:10.1155/2018/2708491 · Cited by 35 · see citing works
“The rising epidemical evidence also shows that obesity is closely related to brain dysfunction and early onset of Alzheimer’s disease [6].”
Background
Administration of the Antioxidant N-Acetyl-Cysteine in Pregnant Mice Has Long-Term Positive Effects on Metabolic and Behavioral Endpoints of Male and Female Offspring Prenatally Exposed to a High-Fat Diet
Berry, A., Bellisario, V., Panetta, P., Raggi, C., Magnifico, M. C., Arese, M., & Cirulli, F. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00048 · Cited by 34 · see citing works
“…oxygen species (ROS; Zhang et al., 2005) and protein oxidation (Souza et al., 2007), thus resulting in increased oxidative damage in the brain (Cecarini et al., 2007; Bruce-Keller et al., 2009; Zhang et al., 2009) and, more in general, in oxidative cell injury (Gutteridge and Halliwell, 2000).”
Background
Dietary influence on central nervous system myelin production, injury, and regeneration
Langley, M. R., Triplet, E. M., & Scarisbrick, I. A. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165779 · Cited by 35 · see citing works
Brain injury caused by HIV protease inhibitors: Role of lipodystrophy and insulin resistance
Gupta, S., Knight, A. G., Losso, B. Y., Ingram, D. K., Keller, J. N., & Bruce‐Keller, A. J. (2012) · Antiviral Research · doi:10.1016/j.antiviral.2012.04.010 · Cited by 35 · see citing works
“Furthermore, epidemiological and experimental studies reveal quite clearly that metabolic dysfunction can increase brain injury and decrease cognitive function (reviewed in (Fillit et al., 2008), (Bruce-Keller et al., 2009), (Haan and Wallace, 2004), (Middleton and Yaffe, 2009)).”
BackgroundSelf-citation
Estradiol Uses Different Mechanisms in Astrocytes from the Hippocampus of Male and Female Rats to Protect against Damage Induced by Palmitic Acid
Frago, L. M., Canelles, S., Freire‐Regatillo, A., Argente-Arizón, P., Barrios, V., Argente, J., García‐Segura, L. M., & Chowen, J. A. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00330 · Cited by 34 · see citing works
Multiple Pathways Involved in Palmitic Acid-Induced Toxicity: A System Biology Approach
Osorio, D., Pinzón, A. M., Martín-Jiménez, C., Barreto, G. E., & González, J. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01410 · Cited by 34 · see citing works
Serotonin transporter gene moderates associations between mood, memory and hippocampal volume
Price, J. S., Strong, J. A., Eliassen, J. C., McQueeny, T. M., Miller, M. M., Padula, C. B., Shear, P. K., & Lisdahl, K. M. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.11.013 · Cited by 33 · see citing works
Hippocampal Lipocalin 2 Is Associated With Neuroinflammation and Iron-Related Oxidative Stress in ob/ob Mice
Jin, Z. H., Kim, K. E., Shin, H. J., Jeong, E. A., Park, K.-A., Lee, J. Y., An, H. S., Choi, E. B., Jeong, J. H., Kwak, W., et al. (2020) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlaa017 · Cited by 33 · see citing works
Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction
Henry, R. J., Barrett, J. P., Vaida, M. L., Khan, N., Makarevich, O. D., Ritzel, R. M., Faden, A. I., & Stoica, B. A. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03107-6 · Cited by 33 · see citing works
“Because mice inherently prefer to explore novel objects, a preference for the novel object (more time than chance [15 s] spent with the novel object) indicates intact memory for the familiar object.”
Background
Sucrose consumption alters steroid and dopamine signalling in the female rat brain
Tobiansky, D. J., Kachkovski, G. V., Enos, R. T., Schmidt, K. L., Murphy, E. A., & Soma, K. K. (2020) · Journal of Endocrinology · doi:10.1530/joe-19-0386 · Cited by 32 · see citing works
Inflammatory Pathways in Overweight and Obese Persons as a Potential Mechanism for Cognitive Impairment and Earlier Onset Alzeihmer’s Dementia in the General Population: A Narrative Review
Costache, A. D., Ignat, B. E., Grosu, C., Maștaleru, A., Abdulan, I. M., Oancea, A., Roca, M., Leon, M. M., Bădescu, M. C., Avadanei-Luca, S., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11123233 · Cited by 29 · see citing works
Relationships between dietary macronutrients and adult neurogenesis in the regulation of energy metabolism
Yon, M. A., Mauger, S. L., & Pickavance, L. C. (2013) · British Journal Of Nutrition · doi:10.1017/s000711451200579x · Cited by 30 · see citing works
Myeloid-specific deletion of NOX2 prevents the metabolic and neurologic consequences of high fat diet
Pepping, J. K., Vandanmagsar, B., Fernandez-Kim, S.-O., Zhang, J., Mynatt, R. L., & Bruce‐Keller, A. J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181500 · Cited by 29 · see citing works
Self-citation
MiR-122 marks the differences between subcutaneous and visceral adipose tissues and associates with the outcome of bariatric surgery
Liao, C., Wang, C., Liu, K., Liu, Y.-Y., Wen, M., & Yeh, T. (2018) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2018.06.005 · Cited by 29 · see citing works
Lopinavir/Ritonavir Treatment Induces Oxidative Stress and Caspaseindependent Apoptosis in Human Glioblastoma U-87 MG Cell Line
Gratton, R., Tricarico, P. M., Guimarães, R. L., Celsi, F., & Crovella, S. (2018) · Current HIV Research · doi:10.2174/1570162x16666180528100922 · Cited by 28 · see citing works
Impact of the principal stroke risk factors on human movements
O’Reilly, C., & Réjean Plamondon, B. (2010) · Human Movement Science · doi:10.1016/j.humov.2010.07.010 · Cited by 27 · see citing works

Authors: Bruce-Keller, A. J., Keller, J. N., & Morrison, C. D.
Affiliations: Pennington Biomedical Research Center (US)
ORCID: Keller, Jeffrey N.
Morrison, Christopher D.
Venue: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher: Elsevier BV
Published: 2009-05
Volume: 1792
Issue: 5
Pages: 395-400
ISSN: 0925-4439 (ISSN-L)
DOI: 10.1016/j.bbadis.2008.10.004
PMC: PMC2699212
OpenAlex: W2154638777
Cited by: 200
References: 124
Citations by year: 2026: 3 · 2025: 8 · 2024: 7 · 2023: 13 · 2022: 5 · 2021: 18 · 2020: 8 · 2019: 14 · 2018: 17 · 2017: 15 · 2016: 16 · 2015: 7 · 2014: 13 · 2013: 14 · 2012: 16
FWCI: 0.92
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1539 d)
Locations: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Civil War Book Review (submittedVersion)
HAL (submittedVersion, other-oa)
Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders: National Institute on Aging (P01AG005119)
National Institute of Neurological Disorders and Stroke (R01NS046267)
Topics: Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: obesity, central nervous system, cognitive decline, metabolic dysfunction, aging, neurodegenerative diseases, animal models of obesity
MeSH terms: Aging, Animals, Brain, Energy Metabolism, Humans, Obesity, Signal Transduction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Obesity and vulnerability of the CNS

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks