title: A dietary fat excess alters metabolic and neuroendocrine responses before the onset of metabolic diseases.
abstract: Early changes in neuroendocrine pathways are essential in the development of metabolic pathologies. Thus, it is important to have a better understanding of the signals involved in their initiation. Long-term consumption of high-fat diets induces insulin resistance, obesity, diabetes. Here, we have investigated early neural and endocrine events in the hypothalamus and hippocampus induced by a short-term high fat, low carbohydrate diet in adult male Wistar rats. The release of serotonin, which is closely associated with the actions of insulin and leptin, was measured, by electrochemical detection following reverse-phase liquid chromatography (HPLC), in the extracellular space of the medial hypothalamus and the dorsal hippocampus in samples obtained from non-anesthetized animals, by microdialysis. The high-fat diet had a specific effect on the hypothalamus. Serotonin release induced by food intake was reduced after 1 week, and effectively ceased after 6 weeks of the diet. After 1 week, there was an increased gene expression of the insulin receptor and the insulin receptor substrates IRS1 and IRS2, as measured by real-time PCR. After 6 weeks of diet, insulin gene expression increased. Leptinemia increased in all cases. This new data support the concept that high-fat diets, in addition to have peripheral effects, cause a rapid alteration in specific central mechanisms involved in energy and glucose homeostasis. The changes in the gene expression of insulin and signaling elements represent possible adaptations aimed at counterbalancing the reduced responsiveness of the serotonergic system to nutritional signals and maintaining homeostasis.
authors.affiliation: CNRS UMR 7059, University Paris 7, 2 place Jussieu, case 7126, 75251 Paris, France.
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Banas
authors.forename: Claude
authors.initials: C
authors.lastname: Rouch
authors.forename: Nadim
authors.initials: N
authors.lastname: Kassis
authors.forename: Eirini M
authors.initials: EM
authors.lastname: Markaki
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Gerozissis
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D008297:Male; D008659:Metabolic Diseases / Q000378:metabolism* / Q000503:physiopathology; D009490:Neurosecretory Systems / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000235:genetics; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004041:Dietary Fats; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D012333:RNA, Messenger; D012701:Serotonin; D011972:Receptor, Insulin; D005947:Glucose
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