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.

Fig. 1

Effect of diet and age on a leptin receptor (ObR), b insulin receptor (IR) and c, d glucocorticoid receptor (GR) in the hypothalamus or hippocampus of male rats fed either a high-fat (HF) or a control (C) diet from postnatal day 22 to the onset of puberty (PUBERTAL), or to postnatal day 90 (ADULT), as depicted by Western blot analysis. Bars represent means ± SEM of the optical density (OD) of receptors’ band divided by that of the respective actin band in each sample. For insulin receptor, the receptor isoforms (IR95 and IR83) were analyzed together. In two-way analysis of variance (ANOVA), # denotes significant effect of diet and $ significant effect of age. Significance was accepted for P < 0.05

Fig. 2

Effect of fat-feeding period on adult animals’ leptin receptor (ObR) levels in the hypothalamus (a) and glucocorticoid receptor (GR) levels in the hippocampus (b), as depicted by Western blot analysis. Adult male rats were fed either Chow (C) or the high-fat (HF) diet. HF diet was provided either from postnatal day (P) 22–P90, or from P22 to puberty onset and then switched to chow, or from puberty onset to P90. Bars represent means ± SEM of the optical density (OD) of receptors’ band divided by that of the respective actin band in each sample. One-way analysis of variance (ANOVA) followed by Dunnett’s two-sided post hoc test; * denotes significant difference from the C diet group. Significance was accepted for P < 0.05