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

Abstract

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 nonobese 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.

Elevated Hypothalamic Glucocorticoid Levels Are Associated With Obesity and Hyperphagia in Male Mice

“…Dependent on the method and duration of corticosterone (Cort) administration, proopiomelanocortin ( Pomc ) expression has both increased (4, 5) and decreased (6) after treatment. Similarly agouti-related protein ( Agrp ) expression follows this inconsistency in response to Cort treatment (7, 8). Although the Gc-response elements (GREs) are present within the promotor regions of Agrp (9), Pomc (10), and neuropeptide Y ( Npy ) (11), the effect of chronic Gc treatment is still unclear.…”

Circannual changes in stress and feeding hormones and their effect on food-seeking behaviors

“…Circulating levels of glucocorticoids, either basal or stress-induced changes, have been shown to influence food choice, body weight and appetite in both humans and animals (Oliver and Wardle, 1999; Baran et al, 2009; Liu et al, 2011; Schwabe and Wolf, 2011) and this may be an important contributing factor to seasonal variation in food intake.…”

“…Animal studies in the laboratory have revealed that, overall, stress-induced changes in circulating glucocorticoids or exogenous administration of glucocorticoids (thereby elevating basal levels) leads to a decrease in food intake (Levine and Morley, 1981; Morley et al, 1983; Liu et al, 2011). In laboratory studies under free-feeding conditions, when rats were administered exogenous glucocorticoids over a period of days, mimicking a chronic elevation in basal levels of glucocorticoids as would be observed in SD, winter months, a decrease in food intake leading to a decrease in body weight was reported (De Vos et al, 1995; Liu et al, 2011).…”

“…In laboratory studies under free-feeding conditions, when rats were administered exogenous glucocorticoids over a period of days, mimicking a chronic elevation in basal levels of glucocorticoids as would be observed in SD, winter months, a decrease in food intake leading to a decrease in body weight was reported (De Vos et al, 1995; Liu et al, 2011). A study by Liu et al (2011) administered a high dose (15 mg/kg/day) and a low dose (5 mg/kg/day) of hydrocortisone to rats to study food intake and body weight change (Liu et al, 2011).…”

“…In laboratory studies under free-feeding conditions, when rats were administered exogenous glucocorticoids over a period of days, mimicking a chronic elevation in basal levels of glucocorticoids as would be observed in SD, winter months, a decrease in food intake leading to a decrease in body weight was reported (De Vos et al, 1995; Liu et al, 2011). A study by Liu et al (2011) administered a high dose (15 mg/kg/day) and a low dose (5 mg/kg/day) of hydrocortisone to rats to study food intake and body weight change (Liu et al, 2011). They found that after chronic administration of the high dose of hydrocortisone (similar to elevated basal levels of circulating glucocorticoids as observed in SD, winter, conditions), food intake was reduced [see also De Vos et al (1995), Konno et al (2008) for similar results of decreased food consumption after dexamethasone treatment].…”