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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.

Background/Aims: Studies conducted in adult rats have shown that increased fat intake affects brain energy homeostasis and stress response. The neuroendocrine circuits controlling the aforementioned functions continue to mature during puberty. The aim of the present study was to investigate whether post-weaning high-fat consumption can modify the endocrine responses of pubertal rats to an acute stress. Methods: Weaning male and female Wistar rats on postnatal day (P) 22 were fed either a high-fat (HF; 45% calories from fat) or a control (10% calories from fat) diet and were sacrificed on the individual day of puberty onset (between P35 and P42) under basal conditions or 4 h after swimming stress. Plasma insulin, leptin and corticosterone levels were determined by radioimmunoassay and the respective receptors in the hypothalamus and hippocampus were determined by Western blot analysis. Results: Stressed HF-fed males showed a smaller increase in plasma insulin levels than chow-fed males. Their leptin receptor levels were reduced in the hypothalamus, but not in the hippocampus, and their glucocorticoid receptor levels were increased in the hypothalamus compared to stressed chow-fed males. HF-fed females were nonresponsive to stress-induced alterations in plasma glucose and corticosterone levels, as well as to hippocampal insulin receptors following stress. Several sex differences were also revealed in the endocrine responses of HF-fed animals following stress. Conclusions: These data show that consumption of high-fat foods during preadolescence can modify the endocrine responses to an acute stress by affecting both stress and metabolic mediators in a sexually dimorphic manner.

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