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

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Obesity and vulnerability of the CNS

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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

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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.

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“It is, however, clear that Western diet and lifestyle are strongly linked to obesity which has been related to cognitive impairment, cognitive decline, and dementia [53, 54].”
A combined X-ray fluorescence and infrared microspectroscopy study for new insights into elemental-biomolecular obesity-induced changes in rat brain structures
Szczerbowska‐Boruchowska, M., Piana, K., Surówka, A. D., Czyżycki, M., Wróbel, P., Szymkowski, M., & Ziomber-Lisiak, A. (2023) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2023.122478 · Cited by 4
Obesity and Systemic Inflammation: Insights into Epigenetic Mechanisms
Kaliman, P., & Párrizas, M. (2011) · InTech eBooks · doi:10.5772/22463 · Cited by 4
“The detrimental effect of obesity on metabolic, cardiovascular and central nervous system dysfunction is well documented, as is its association with type 2 diabetes and cancer (Andersson et al., 2008; Bruce-Keller et al., 2009; Gallagher and LeRoith, 2010).”
Background
PREVALENCE OF OBESITY AMONG MUSCULOSKELETAL PATIENTS
Uddin, M. S., Hossain, M. M., Islam, M. S., Haque, M. O., Kulsum, U., Rahman, E., Rahman, M. H., & Patwary, M. F. K. (2015) · International Journal of Physiotherapy and Research · doi:10.16965/ijpr.2015.104 · Cited by 4
“8% to 66%, with most of this rise occurring since 1980 [3].”
Background
Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunctionPreprint
Henry, R., Barrett, J. P., Vaida, M., Khan, N. Z., Makarevich, O., Ritzel, R., Faden, A., & Stoica, B. (2023) · bioRxiv · doi:10.1101/2023.07.28.550986 · Cited by 12
“Activation of brain and peripheral inflammation pathways is a key pathophysiological feature in both TBI [8-12] and obesity [12-20] and has been implicated in the development of associated neurological dysfunction [8, 21, 22].”
Background
Altered gray matter structural covariance networks in young adults with obesity
Xu, H., Xu, C., & Xu, J. (2024) · International Journal of Obesity · doi:10.1038/s41366-024-01703-3 · Cited by 3
“These ﬁ ndings indicate the adverse effect of obesity might be associated with the altered triple networks.”
Preliminary Exploration on the Effects of a Novel Antidepressant Formula Food in a Mouse Model
Chen, X., Mao, R., Zou, Y., Yue, W., Dong, W., & Zhang, Y. (2025) · Foods · doi:10.3390/foods14091640 · Cited by 3
Association between changes in obesity status and neuropsychiatric health and brain structure in different glucose status
Chen, P., Zhang, P., Lin, Z., Qiu, J., Zou, M., Liu, R., Huang, L., & Sun, W. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1676168 · Cited by 3
Assessment of visual and auditory evoked potentials in young obese males
Narra, L. K., Ghate, J. R., Sinha, M., & Sinha, R. (2020) · Medical Journal Armed Forces India · doi:10.1016/j.mjafi.2020.08.017 · Cited by 3
Chronic increase in sugar consumption and visual attention in Wistar rats
Lange, K. W., Hauser, J., Kaunzinger, I., Nakamura, Y., Reißmann, A., Stollberg, E., Guo, J., & Li, S. (2018) · Journal of Food Bioactives · doi:10.31665/jfb.2018.3159 · Cited by 3
“Obesity has been shown to be associated with cognitive impairment and an increased risk of dementia (Haslam and James, 2005; Bruce-Keller et al., 2009; Dye et al., 2017).”
Background
A comparative study of audio and visual reaction time in obese and non-obese subjects
Munawar, A., & Aleem, A. (2021) · Asian Journal of Medical Sciences · doi:10.3126/ajms.v12i4.32916 · Cited by 3
Obesity, Cancer and Psychopathology: Can Vegetarian Diet Be of Help?
Kumar, V., Thakur, A. K., & Chatterjee, S. S. (2012) · Springer eBooks · doi:10.1007/978-94-007-2923-0_18 · Cited by 2
Single dose and repeated administrations of liraglutide alter energy metabolism in the brains of young and adult rats
Prá, M. D., Ferreira, G. K., de Mello, A. H., Schraiber, R. D. B., Cardoso, L. C., Souza, L. D. R., da Rosa, N., Fortunato, J. J., & Rezin, G. T. (2016) · Biochemistry and Cell Biology · doi:10.1139/bcb-2016-0016 · Cited by 2
“2010), as well as by endocrine disorders, which alter energy homeostasis (Bruce-Keller et al. 2009).”
Background
Effect modification by dietary patterns in the relationship between slow gait and incident depressive symptoms: a 6-year cohort study of older Japanese adults (NISSIN Project)
Hao, W., Shan, Y., Kimura, T., Ukawa, S., Ohira, H., Okabayashi, S., Wakai, K., Ando, M., & Tamakoshi, A. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1698581 · Cited by 1
Assessment of Auditory and Visual Reaction Time in Healthy Obese Individuals
Grewal, S., Gupta, V., Walia, L., & Sekhon, T. S. (2013) · Journal Of Advance Researches In Medical Sciences · Cited by 1
A Novel Spatiotemporal Longitudinal Methodology for Predicting Obesity Using Near Infrared Spectroscopy (NIRS) Cerebral Functional Activity Data
Abdullah, A., Hussain, A., & Khan, I. H. (2018) · Cognitive Computation · doi:10.1007/s12559-017-9541-x · Cited by 1
“Figure-2: Link between BMI, diabetes and coronary heart disease [7]”
Background
A correlation between height, obesity and intelligence in South Indian medical students
Fathima, S. S., Francis, Y. M., Francis, Y. M., Kumar, S., Balaji, K. C., Raghunath, G., & Kumaresan, M. (2021) · Biomedicine · doi:10.51248/.v41i1.552 · Cited by 1
“1: 2021 diabetes mellitus, hypertension, heart disease, dyslipidaemia, cerebrovascular disease, certain types of cancer and other diseases (2).”
Background
Propentofylline decreases hypothalamic astrogliosis induced by hypercaloric diet in the rat
Bondan, E. F., Vieira, C., Martins, M. D. F. M., Kirsten, T. B., & Bernardi, M. M. (2018) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x20180019 · Cited by 1
Long-Term Weight Gain and Prevalence of Obesity in General Adult Psychiatric Inpatients
Lazzari, C. G. (2018) · American Journal of Psychiatry and Neuroscience · doi:10.11648/j.ajpn.20180603.16 · Cited by 1
“One suggestion proposed to overcome these effects is the use of non-steroidal anti-inflammatory drugs and ω-3 fatty acids to promote the growth of helpful intestinal bacteria in patients at risk of high BMI and psychiatric disorders [71] thus having beneficial effects on mental health [72].”
Background
Anti-Inflammatory and Neuroprotective Effect of the Anti-Obesity Dietary Supplement Dekosilhue® in an In Vitro Model of Neuroinflammation
Borgonetti, V., Cenci, L., & Galeotti, N. (2022) · Nutraceuticals · doi:10.3390/nutraceuticals2010002 · Cited by 1
“Although these diseases have different etiologies and pathophysiological manifestations, they all share a neuroinflammatory component [5] and obese patients represent a population that is more prone to develop central disorders [6].”
Background
Central lipid detection and the regulation of feeding behavior
Cansell, C., & Luquet, S. H. (2013) · Oléagineux Corps gras Lipides · doi:10.1051/ocl.2013.0500
“In fact, there is increasing evidence that obesity is associated with impairment on certain cognitive function, such as executive function, attention and memory (Gunstad et al., 2007; Bruce-Keller et al., 2009; Bruehl et al., 2009).”
Background
Risk factors of development of low back pain for the patients attended at CRP
Biswas, S. S. (2013)
Case Study Report on Obesity with Resisted Exercises Versus Resisted Exercises and Diet
Subramanian, D. S. S. (2016) · Journal of Medical Science And clinical Research · doi:10.18535/jmscr/v4i6.40
What are the Effects of Maternal Obesity on Synaptic Function in the Maternal and Offspring Hippocampus
Lau, D. (2013) · UWSpace (University of Waterloo)
Studies on the Development and Consequences of Neuroinflammation in Obesity
Buckman, L. B. (2014)
The Role of NADPH oxidase 2 (NOX2) in High-Fat Diet-Induced Adiposopathy and Brain Dysfunction in a Mouse Model
Pepping, J. K. (2016) · Louisiana State University · doi:10.31390/gradschool_theses.1329
“…models of obesity (Bruce-Keller et al., 2010; Chinen et al., 2007; Zhang et al., 2005) and are also in agreement with the growing body of literature describing the sensitivity of the brain to obesity-induced metabolic dysfunction (reviewed in (Bruce-Keller et al., 2009; Middleton and Yaffe, 2009)).”
Result
A Comparaison between Personality Traits and Eating Behavior among Women with High and Normal Body Mass Index
Shahsavari, M., Fathi-Ashtiani, A., & Tabatabae, K. R. (2017)
Predicting Obesity Using Longitudinal Near Infra-Red Spectroscopy (NIRS) Data
Abdullah, A., Hussain, A., & Khan, I. H. (2017) · International Conference on Compute and Data Analysis (ICCDA) · doi:10.1145/3093241.3093286
“Over the last decade, a number of studies have described changes and decrease in whole brain volume of overweight/obese individuals [5, 6, 7].”
Background
Beliefs about the Impact of Excess Body Weight on Biopsychosocial Functioning in Multiple Sclerosis Patients
Ness, A. R. (2017) · MOspace Institutional Repository (University of Missouri)
Adipocytokines: A Potential Link Between Obesity and CNS Disorders
Hafizi, N., Alipoor, E., & Hosseinzadeh-Attar, M. (2017) · Obesity Research - Open Journal · doi:10.17140/oroj-4-e011
Pleiotropic effects drive correlation between body mass index and cortical myelinationPreprint
Ronan, L., Medic, N., & Fletcher, P. C. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/274134
Role of Mitochondria in Neurodegeneration in Obesity and Type 2 Diabetes
Cardoso, S., Seiça, R. M. F., & Moreira, P. I. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-811752-1.00013-4
Efecto de un programa de restricción calórica sobre la memoria de trabajo y clasificación en un estudio de caso
Betancourt, J. T. S., Meza-Amaya, A., & Segura-Romero, A. K. (2021) · DIVULGARE Boletín Científico de la Escuela Superior de Actopan · doi:10.29057/esa.v8i16.6875
Metabolic Surgery and Chronic Traumatic Encephalopathy: Perceptions of Former NFL Players
McGlennon, T. W., Roberts, A. J., Buchwald, J. N., Pories, W. J., Ahnfeldt, E. P., Perryman, S. V., Greimel, S., & Buchwald, H. (2024) · Obesity Surgery · doi:10.1007/s11695-024-07475-z
“Prior research has linked obesity to cognitive decline and enhanced vulnerability to brain injury [13–15].”
Study of the effect and mechanisms of Zhi-Zi-Chi-Tang on the cognitive dysfunction in db/db mice
Deng, J., Sun, J., Peng, C., Yang, M., Wang, Z., Liang, Y., & Zhang, H. (2025) · Journal of Functional Foods · doi:10.1016/j.jff.2025.106886
The role of NEDD4L in metabolic dysfunction-associated fatty liver disease (MAFLD) by regulating ferroptosis via deubiquitinating the TGF-β receptor TβRII
Li, F., Yao, J., Yao, J. S., Mou, Y., Li, D., & Wei, L. (2025) · Biochemistry and Cell Biology · doi:10.1139/bcb-2025-0175
Additional file 1 of 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) · Figshare · doi:10.6084/m9.figshare.26714257
Obesity Aggravates Status Epilepticus Through Lipocalin-2-mediated Inflammation and Necroptosis
Lee, G. S., Lee, S. B., Kim, M.-H., Roh, G. S., Kim, M. J., & Kim, H. J. (2026) · Neurochemical Research · doi:10.1007/s11064-025-04648-9
“Increasing evidence implicates obesity as a risk factor for neurodegenerative disorders, including Alzheimer’s disease and mild cognitive impairment [ 2–5].”
Postinjury Carnosine Treatment Prevents Neurotrophic Factor Decline in Denervated Muscle and Spinal Cord After Traumatic Injury
Kuchárová, K., Kuruc, T., Magurova, M., Ihnátová, L., Ileninová, M., Kisucká, A., Gálik, J., & Lukáčová, N. (2026) · European Journal of Neuroscience · doi:10.1111/ejn.70461
“These rats have an atypical baseline metabolic and inflammatory state characterized by increased inflammation, elevated reactive oxygen species (ROS) production and lipid peroxidation (Varanoske et al. 2017; Bruce-Keller et al. 2009; Patel et al. 2023).”
Rôle de la résistine hypothalamique dans l'installation de l’inflammation hypothalamique et l’insulino-résistance : impact de la consommation aigüe ou chronique d'un régime hyper lipidique
Rifai, S. A. (2019) · theses.fr (ABES) · doi:10.70675/9fe74603z0a55z460cz9ce8z7bf7f41fd839
Adipose Tissue–Central Nervous System Axis in Obesity: Molecular Mechanisms, Inflammation, and Nutritional and Technological Implications
Castelli, S., Aiello, G., Bruno, A. D., Fratantonio, D., Tripodi, G., Aiello, V., Lombardo, M., & Baldelli, S. (2026) · Metabolites · doi:10.3390/metabo16080533

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 › Endocrinology, Diabetes and Metabolism › 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

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Obesity and vulnerability of the CNS

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