Fat Feeding of Rats During Pubertal Growth Leads to Neuroendocrine Alterations in Adulthood

Abstract

Juvenile obesity is a rising epidemic due largely to consumption of caloric dense, fat-enriched foods. Nevertheless, literature on fat-induced neuroendocrine and metabolic disturbances during adolescence, preceding obesity, is limited. This study aimed to examine early events induced by a fat diet (45% calories from saturated fat) in male rats fed the diet during the pre- and post-pubertal period. The neuroendocrine endpoints studied were the levels of circulating leptin, insulin and corticosterone, as well as their receptors in the hypothalamus and hippocampus. Hormonal levels were determined by radioimmunoassay and receptors' levels by western blot analysis. Leptinemia was increased in pubertal rats and in adult rats fed the fat diet from weaning to adulthood, but not in those fed from puberty to adulthood. Modifications in the developmental pattern from puberty to adulthood were observed for most of the brain receptors studied. In adult animals fed the fat diet from weaning onwards, the levels of leptin receptors in the hypothalamus and glucocorticoid receptors in the hippocampus were decreased compared to chow-fed controls. Switching from fat to normal chow at puberty onset restored the diet-induced alterations on circulating leptin, but not on its hypothalamic receptors. These data suggest that when a fat-enriched diet, resembling those consumed by many teenagers, provided in rats during pubertal growth, it can longitudinally influence the actions of leptin and corticosterone in the brain. The observed alterations at a preobese state may constitute early signs of the disturbed energy balance toward overweight and obesity.

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

“…This receptor system has been shown to be responsive to various stressors [9,10,11]. Additionally, the levels of circulating corticosterone and limbic GR receptors are subject to changes following either short-term [6,12] or prolonged fat consumption [3,13,14]. Furthermore, through its key role on glucose availability, corticosterone exhibits significant interplay with hormonal regulators of energy balance, such as insulin and leptin [15,16].…”

“…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]. Leptin receptor downregulation in the hypothalamus appears as an early sign of a HF diet-induced disturbance in the rat [13,14]. …”

“…Metabolic manipulations during juvenility, such as application of a HF diet, can also modify the behavior and basal HPA axis activity of the rats at the onset of puberty [28]. We have recently shown that pubertal animals fed a HF diet exhibit, under basal conditions, an altered neuroendocrine status regarding peripheral metabolic regulators and their brain receptors [13,14]. In brief, HF-fed males show increased leptinemia at the onset puberty, while the respective females have reduced insulin and increased corticosterone levels, accompanied by decreased GR levels in the hypothalamus.…”

Exaggerated activity of HPA axis in obese rats fed normocaloric liquid nutrition

“…the plasma cort levels correlate with the degree of obesity. therefore, we suggest that obesity induced by fresubin in adulthood is further promoted by cort-induced remodeling of adipose tissue [3] and also by the stimulation of overconsumption through positive feedback mechanisms that enhances the drive for hedonic response to high-sweet or fatty foods [6]. However, consumption of diet rich in fats for 6 weeks has not effect on the activation of HPa axis [21].…”

“…at the same time, however, increased cort levels may participate in the development of obesity [5,16] and, in contrast to the suppression of food intake by acute increase in cort levels, long-term elevation in cort levels stimulates food intake and promote adipocyte differentiation [3,6,11,19].…”