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.

Deleterious effects of lard-enriched diet on tissues fatty acids composition and hypothalamic insulin actions

“…After 8 weeks of dietary treatment, HF rats showed increased fasting glycaemia alongside normoinsulinemia, which suggests the development of peripheral insulin resistance, in agreement with previous studies (40,48). The type of fat appears to be decisive for the development of insulin resistance: mice treated with either MUFA or SFA rich diets showed increased body mass, but only those treated with SFA developed glucose intolerance (49).…”

“…The anorexigenic effects of insulin are decisive for the maintenance of body energy homeostasis, and deficient insulin signalling has been associated with obesity in various experimental models (6,48,58). In the present study, we examined whether a 8 weeks lard-enriched dietary intervention affected food intake after insulin intracerebroventricular administration.…”

A review of lifestyle factors that contribute to important pathways associated with major depression: Diet, sleep and exercise

“…In animal studies, semistarvation on a high carbohydrate or protein diet affected serotonin turnover in the brain (Schweiger et al, 1989). In addition, the consumption of sugar as part of a meal (Inam et al, 2006) or eating a high-carbohydrate diet (Buwalda et al, 2001) influenced 5-HT1A receptor sensitivity; and one week on a high fat, low carbohydrate diet decreased serotonin release in the hypothalamus (Banas et al, 2009). In contrast, the acute intake of a carbohydrate-rich food increased brain tryptophan and consequent brain serotonin levels (Fernstrom and Wurtman, 1971).…”

High-Fat Feeding Influences the Endocrine Responses of Pubertal Rats to an Acute Stress

“…These hormones convey metabolic information to the brain and control disturbances in energy homeostasis [17,18]. Dietary fat can significantly modify their levels in the periphery and their signaling in the brain [19,20]. Central resistance to leptin or insulin, in combination with peripheral changes in the levels of these hormones is a common feature of the obese state [21].…”