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Liu, J.* ; Dimitrov, S. ; Sawangjit, A.* ; Born, J. ; Ehrlich, I.* ; Hallschmid, M.

Short-term high-fat feeding induces a reversible net decrease in synaptic AMPA receptors in the hypothalamus.

J. Nutr. Biochem. 87:108516 (2021)

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Dietary obesity compromises brain function, but the effects of high-fat food on synaptic transmission in hypothalamic networks, as well as their potential reversibility, are yet to be fully characterized. We investigated the impact of high-fat feeding on a hallmark of synaptic plasticity, i.e., the expression of glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) that contain the subunits GluA1 and GluA2, in hypothalamic and cortical synaptoneurosomes of male rats. In the main experiment (experiment 1), three days, but not one day of high-fat diet (HFD) decreased the levels of AMPAR GluA1 and GluA2 subunits, as well as GluA1 phosphorylation at Ser845, in hypothalamus but not cortex. In experiment 2, we compared the effects of the three-day HFD with those a three-day HFD followed by four recovery days of normal chow. This experiment corroborated the suppressive effect of high-fat feeding on hypothalamic but not cortical AMPAR GluA1, GluA2, and GluA1 phosphorylation at Ser845, and indicated that the effects are reversed by normal-chow feeding. High-fat feeding generally increased energy intake, body weight, and serum concentrations of insulin, leptin, free fatty acids, and corticosterone; only the three-day HFD increased wakefulness assessed via video analysis. Results indicate a reversible down-regulation of hypothalamic glutamatergic synaptic strength in response to short-term high-fat feeding. Preceding the manifestation of obesity, this rapid change in glutamatergic neurotransmission may underlie counter-regulatory efforts to prevent excess body weight gain, and therefore, represent a new target of interventions to improve metabolic control.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Ampa Receptor Signaling ; Cortex ; High-fat Diet ; Hypothalamus ; Sleep/wakefulness ; Synaptic Plasticity; Saturated Fat; Memory Consolidation; Neuronal Plasticity; Melanocortin System; Neurotrophic Factor; Sleep; Diet; Subunit; Obesity; Wake

ISSN (print) / ISBN 0955-2863

e-ISSN 0955-2863

Journal Journal of Nutritional Biochemistry, The

Quellenangaben Volume: 87, Article Number: 108516

Publisher Elsevier

Publishing Place Ste 800, 230 Park Ave, New York, Ny 10169 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)

Grants Bundesministerium für Bildung und Forschung
China Scholarship Council