The Insulin Effect on Cerebrocortical Theta Activity Is Associated with Serum Concentrations of Saturated Nonesterified Fatty Acids
Abstract
Context: Insulin action in the brain contributes to adequate regulation of body weight, neuronal survival, and suppression of endogenous glucose production. We previously demonstrated by magnetoencephalography in lean humans that insulin stimulates activity in beta and theta frequency bands, whereas this effect was abolished in obese individuals. Objective: The present study aims to define metabolic signals associated with the suppression of the cerebrocortical response in obese humans. Design and Setting: We determined insulin-mediated modulation of spontaneous cerebrocortical activity by magnetoencephalography during a hyperinsulinemic euglycemic clamp and related it to measures of ectopic fat deposition and mediators of peripheral insulin resistance. Visceral fat mass and intrahepatic lipid content were quantified by magnetic resonance imaging and spectroscopy. Multiple regression analysis was used to analyze associations of cerebrocortical insulin sensitivity and metabolic markers related to obesity. Participants: Forty-nine healthy, nondiabetic humans participated in the study. Results: In a multiple regression, insulin-mediated stimulation of theta activity was negatively correlated to body mass index, visceral fat mass, and intrahepatic lipid content. Although fasting saturated nonesterified fatty acids mediated the correlations of theta activity with abdominal and intrahepatic lipid stores, adipocytokines displayed no independent correlation with insulin-mediated cortical activity in the theta frequency band. Conclusions: Thus, insulin action at the level of cerebrocortical activity in the brain is diminished in the presence of elevated levels of saturated nonesterified fatty acids. High serum concentrations of saturated nonesterified fatty acids are associated with a decreased insulin effect on cortical activity in the human brain.
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Other factors such as genetic background, elevated circulating free fatty acids and impaired insulin transport across the blood-brain barrier have also been implicated in brain insulin resistance.
“although other factors, such as genetic background19, elevated circulating free fatty acids20 and impaired insulin transport across the blood–brain barrier21,22, have also been implicated.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [20]
A sample size of N = 10 was calculated for the hyperinsulinemic-euglycemic clamp study (α = 0.05, power = 0.9) based on an effect size of Cohen's dz = 1.178 from previous work in lean men.
“For the hyperinsulinemic–euglycemic clamp study, a sample size of N = 10 was calculated (α = 0.05, power (1 – β error probability) = 0.9, G*Power) based on an effect size of Cohen’s dz = 1.178, which was achieved in our previous work investigating glucose infusion rate in response to intranasal insulin in lean men20.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [20]
Cites
1 retracted
Tsukumo, D. M. L., Carvalho-Filho, M. A., Carvalheira, J. B. C., Prada, P. O., Hirabara, S. M., Schenka, A. A., Araújo, E. P., Vassallo, J., Curi, R., Velloso, L. A., et al. (2007) · Diabetes · doi:10.2337/db06-1595 · Cited by 826 · see citing works
RetractedPositional 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
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326 · see citing works
Effects of the <i>obese</i> Gene Product on Body Weight Regulation in <i>ob</i> / <i>ob</i> Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017 · see citing works
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690 · see citing works
The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
Berg, A. H., Combs, T. P., Du, X., Brownlee, M., & Scherer, P. E. (2001) · Nature Medicine · doi:10.1038/90992 · Cited by 2,526 · see citing works
Direct transesterification of all classes of lipids in a one-step reaction.
Lepage, G., & ROY, C. C. (1986) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38861-1 · Cited by 2,385 · see citing works
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728 · see citing works
The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus
Eizirik, D. L., Cardozo, A. K., & Cnop, M. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0015 · Cited by 1,173 · see citing works
Milanski, M., Degasperi, G., Coope, A., Morari, J., Denis, R., Cintra, D. E., Tsukumo, D. M. L., Anhe, G., Amaral, M. E., Takahashi, H. K., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2760-08.2009 · Cited by 1,125 · see citing works
Laufs, H., Krakow, K., Sterzer, P., Eger, E., Beyerle, A., Salek-Haddadi, A., & Kleinschmidt, A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1831638100 · Cited by 1,028 · see citing works
Endogenous glucose production is inhibited by the adipose-derived protein Acrp30
Combs, T. P., Berg, A. H., Obici, S., Scherer, P. E., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14120 · Cited by 935 · see citing works
Splanchnic lipolysis in human obesity
Nielsen, S., Guo, Z., Johnson, C. M., Hensrud, D. D., & Jensen, M. D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21047 · Cited by 933 · see citing works
Ceramides in insulin resistance and lipotoxicity
Summers, S. A. (2005) · Progress in Lipid Research · doi:10.1016/j.plipres.2005.11.002 · Cited by 852 · see citing works
Suganami, T., Tanimoto-Koyama, K., Nishida, J., Itoh, M., Yuan, X., Mizuarai, S., Kotani, H., Yamaoka, S., Miyake, K., Aoe, S., et al. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000251608.09329.9a · Cited by 806 · see citing works
Images of desire: food-craving activation during fMRI
Pelchat, M. L., Johnson, A., Chan, R., Valdez, J., & Ragland, J. D. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.08.023 · Cited by 667 · see citing works
Bays, H., Mandarino, L., & DeFronzo, R. A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030723 · Cited by 664 · see citing works
Key enzyme in leptin-induced anorexia
Niswender, K. D., Morton, G. J., Stearns, W. H., Rhodes, C. J., Myers, M. G., & Schwartz, M. W. (2001) · Nature · doi:10.1038/35101657 · Cited by 585 · see citing works
Plasma Adiponectin Concentrations Predict Insulin Sensitivity of Both Glucose and Lipid Metabolism
Tschritter, O., Fritsche, A., Thamer, C., Haap, M. M., Shirkavand, F., Rahe, S., Staiger, H., Maerker, E., Häring, H. U., & Stümvoll, M. (2003) · Diabetes · doi:10.2337/diabetes.52.2.239 · Cited by 585 · see citing works
Self-citationCauses and Metabolic Consequences of Fatty Liver
Stefan, N., Kantartzis, K., & Häring, H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0009 · Cited by 529 · see citing works
Self-citationBoden, 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
Theta oscillations index human hippocampal activation during a working memory task
Tesche, C. D., & Karhu, J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.919 · Cited by 497 · see citing works
Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus
Niswender, K. D., Morrison, C. D., Clegg, D. J., Olson, R., Baskin, D. G., Myers, M. G., Seeley, R. J., & Schwartz, M. W. (2003) · Diabetes · doi:10.2337/diabetes.52.2.227 · Cited by 476 · see citing works
Tissue-Specific mRNA Expression Profiles of Human Toll-Like Receptors and Related Genes
Nishimura, M., & Naito, S. (2005) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.28.886 · Cited by 443 · see citing works
Kelley, D. E., McKolanis, T. M., Hegazi, R. A. F., Kuller, L. H., & Kalhan, S. C. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00117.2003 · Cited by 426 · see citing works
Effect of long chain triglyceride infusion on glucose metabolism in man
Thiébaud, D., DeFronzo, R. A., Jacot, E., Golay, A., Acheson, K. J., Maeder, E., Jéquier, E., & Felber, J. (1982) · Metabolism · doi:10.1016/0026-0495(82)90163-9 · Cited by 296 · see citing works
Standardized assessment of whole body adipose tissue topography by MRI
Machann, J., Thamer, C., Schnoedt, B., Haap, M., Haring, H., Claussen, C., Stumvoll, M., Fritsche, A., & Schick, F. (2005) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.20292 · Cited by 266 · see citing works
Self-citationTschritter, O., Preissl, H., Hennige, A. M., Stumvoll, M., Porubska, K., Frost, R., Marx, H., Klösel, B., Lutzenberger, W., Birbaumer, N., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604404103 · Cited by 223 · see citing works
Self-citationThe Modulation of Inflammatory Gene Expression by Lipids: Mediation through Toll-like Receptors
Lee, J. Y., & Hwang, D. H. (2006) · Molecules and Cells · doi:10.1016/s1016-8478(23)12877-9 · Cited by 195 · see citing works
Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans.
Roden, M., Krššák, M., Stingl, H., Gruber, S., Hofer, A., Fürnsinn, C., Moser, E., & Waldhäusl, W. K. (1999) · Diabetes · doi:10.2337/diabetes.48.2.358 · Cited by 189 · see citing works
A Model for Fatty Acid Transport into the Brain
Hamilton, J. A., & Brunaldi, K. (2007) · Journal of Molecular Neuroscience · doi:10.1007/s12031-007-0050-3 · Cited by 176 · see citing works
Seppala-Lindroos, A. (2002) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.7.3023 · Cited by 168 · see citing works
Staiger, K., Staiger, H., Weigert, C., Haas, C., Häring, H., & Kellerer, M. (2006) · Diabetes · doi:10.2337/db06-0188 · Cited by 139 · see citing works
Fatty Acid-Binding Proteins of Nervous Tissue
Veerkamp, J. H., & Zimmerman, A. W. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:16:2-3:133 · Cited by 135 · see citing works
Variation in the FTO gene locus is associated with cerebrocortical insulin resistance in humans
Tschritter, O., Preissl, H. T., Yokoyama, Y., Machicao, F. E., Häring, H., & Fritsche, A. (2007) · Diabetologia · doi:10.1007/s00125-007-0839-1 · Cited by 114 · see citing works
Self-citationExpression of free fatty acid receptor GPR40 in the central nervous system of adult monkeys
Ma, D., Tao, B., Warashina, S., et al. (2007) · Neuroscience Research · doi:10.1016/j.neures.2007.05.001 · Cited by 110 · see citing works
Plasma Adiponectin and Endogenous Glucose Production in Humans
Stefan, N., Stümvoll, M., de Courten, B. V., Weyer, C., Funahashi, T., Matsuzawa, Y., Bogardus, C., & Tataranni, P. A. (2003) · Diabetes Care · doi:10.2337/diacare.26.12.3315 · Cited by 106 · see citing works
Self-citationHennige, A. M., Stefan, N., Kapp, K., Lehmann, R., Weigert, C., Beck, A., Moeschel, K., Mushack, J., Schleicher, E. D., & Häring, H. (2006) · The FASEB Journal · doi:10.1096/fj.05-4635fje · Cited by 94 · see citing works
Self-citationVigilance and EEG power in rats: effects of potent inhibitors of the neuronal nitric oxide synthase
Dzoljic, E. D., van Leeuwen, R., VRIES, R. D., & Dzoljic, M. (1997) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/pl00005028 · Cited by 42 · see citing works
Hennige, A. M., Sartorius, T., Lutz, S. Z., Tschritter, O., Preissl, H., Hopp, S., Fritsche, A., Rammensee, H.-G., Ruth, P., & Häring, H.-U. (2009) · Diabetologia · doi:10.1007/s00125-009-1522-5 · Cited by 41 · see citing works
Self-citationInsulin effects on beta and theta activity in the human brain are differentially affected by ageing
Tschritter, O., Hennige, A. M., Preissl, H. T., Grichisch, Y., Kirchhoff, K., Kantartzis, K., Machicao, F. E., Fritsche, A., & Häring, H. (2008) · Diabetologia · doi:10.1007/s00125-008-1187-5 · Cited by 27 · see citing works
Self-citationInsulin Secretion: Fatty Acid Signalling via Serpentine Receptors
Rutter, G. A. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00322-1 · Cited by 13 · see citing works
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Self-citationOtt, V., Benedict, C., Schultes, B., Born, J., & Hallschmid, M. (2012) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01490.x · Cited by 139 · see citing works
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Self-citationSartorius, T., Ketterer, C., Kullmann, S., Balzer, M., Rotermund, C., Binder, S., Hallschmid, M., Machann, J., Schick, F., Somoza, V., et al. (2012) · Diabetes · doi:10.2337/db11-1521 · Cited by 73 · see citing works
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Hummel, J., Benkendorff, C., Fritsche, L., Prystupa, K., Vosseler, A., Gancheva, S., Trenkamp, S., Birkenfeld, A. L., Preissl, H., Roden, M., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00869-w · Cited by 48 · see citing works
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Self-citation
- Authors
- Tschritter, O., Preissl, H., Hennige, A. M., Sartorius, T., Grichisch, Y., Stefan, N., Guthoff, M., Düsing, S., Machann, J., Schleicher, E., Cegan, A., Birbaumer, N., Fritsche, A., & Häring, H.-U.
- Affiliations
- University of Tübingen (DE)
- University of Arkansas for Medical Sciences (US)
- Department of Internal Medicine IV (O.T., A.M.H., T.S., Y.G., N.S., M.G., S.D., E.S., A.C., A.F., H.-U.H.), University Hospital, University of Tübingen, 72076 Tübingen, Germany
- Section on Experimental Radiology (J.M.), Department of Diagnostic Radiology, University of Tübingen, 72076 Tübingen, Germany
- IRCCS San Camillo Hospital (IT)
- Corresponding author
- Tschritter, Otto
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-11-01
- Volume
- 94
- Issue
- 11
- Pages
- 4600-4607
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1968074115
- Cited by
- 42
- References
- 42
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 6 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 2 · 2013: 4 · 2012: 3
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin, obesity, hyperinsulinemic-euglycemic clamp, visceral fat, intrahepatic lipid, adipokines, body mass index, brain glucose metabolism
- MeSH terms
- Adipose Tissue, Adult, Blood Glucose, Cerebral Cortex, Fasting, Fatty Acids, Nonesterified, Female, Humans, Hyperinsulinism, Insulin, Lipids, Male, Obesity, Theta Rhythm, Magnetoencephalography, Glucose Clamp Technique, Waist-Hip Ratio
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