Glucocorticoids decrease body weight and food intake and inhibit appetite regulatory peptide expression in the hypothalamus of rats

Abstract

The aim of the present study was to investigate the effects of glucocorticoids (GCs) on appetite and gene expression of the hypothalamic appetite regulatory peptides, neuropeptide Y (NPY), agouti-related protein (AGRP) and cocaine and amphetamine-regulated transcript (CART), in non-obese and obese rats. Both non-obese and obese rats were randomly assigned to three groups: normal saline, low- and high-dose GC groups (NSG, LDG and HDG, respectively), which received an intraperitoneal injection with normal saline (0.2 ml/100 g) or hydrocortisone sodium succinate at 5 and 15 mg/kg, respectively, for 20 days. The expression levels of NPY, AGRP and CART mRNA in the hypothalamus were measured by real-time quantitative PCR. Non-obese and obese rats were found to undergo weight loss after GC injection, and a higher degree of weight loss was observed in the HDG rats. The average and cumulative food intakes in the obese and non-obese rats injected with high-dose GC were lower compared to that in the NSG (p<0.05). mRNA expression levels of the orexigenic neuropeptides, NPY and AGRP, and the anorexigenic neuropeptide, CART, were significantly lower in the HDG than levels in the NSG for both the obese and non-obese rats (p<0.05). GC treatment decreased appetite and body weight, induced apparent glucolipid metabolic disturbances and hyperinsulinemia, while down-regulated mRNA expression levels of the orexigenic neuropeptides, NPY and AGRP, and anorexigenic neuropeptide, CART, in the hypothalamus in the rats. The mechanism which induces this neuropeptide expression requires further study.

Figure 1.

Effect of GC on body weight and cumulative food intake in rats. High-dose GC (15 mg/kg/day) reduced body weight in both (A) non-obese rats from the 5th day of injection and (B) obese rats from the 2nd day, and these differences lasted until the end of treatment. High-dose GC inhibited food intake in both (C) non-obese rats from the 16th day and (D) obese rats from the 10th day, and the significance of the effect lasted to the end of the treatment. After low-dose GC treatment (5 mg/kg/day), neither body weight nor cumulative food intake was significantly different from that of the NSG (^*p<0.05, ^**p<0.01). NSG, normal saline group; LDG, low-dose glucocorticoid group (5 mg/kg/day); HDG, high-dose glucocorticoid group (15 mg/kg/day).

Figure 2.

Effect of GC on NPY, AGRP and CART gene expression in the hypothalamus of rats. Non-obese rats (NSG, n=12; LDG and HDG, n=13), Obese rats (NSG and LDG, n=13; HDG, n=14). NSG, normal saline group; LDG, low-dose glucocorticoid group (5 mg/kg/day); HDG, high-dose glucocorticoid group (15 mg/kg/day). Data are expressed as the means ± SEM of the NSG. ^*p<0.05, ^**p<0.01.