Glucocorticoid-dependent stimulation of adiposity and appetite by a ghrelin mimetic in the rat

Abstract

Objective: Chronic administration of GH secretagogues (GHSs) induces a state of positive energy balance in rodents by a GH-independent mechanism. Here we sought to determine to what extent the GHS effects to increase food intake and increase fat accumulation are glucocorticoid-dependent. Design: The effects of twice-daily s.c. injections of GH-releasing peptide-6 (GHRP-6) (250 mg/kg) for 2 weeks on body weight, food intake and fat pad weight were determined in both adrenalectomised (ADX) rats (with or without basal corticosterone replacement) and adrenal-intact rats. Results: All GHS-injected rats had a significantly increased body weight at the end of 2 weeks of treatment compared with saline controls. However, increased fat accumulation was only seen in adrenalintact rats, with a 15% increase in s.c. inguinal (P , 0.05 vs saline controls) and 20% increase in visceral mesenteric (P , 0.05) fat pad weights following GHS treatment. The increased body weight observed in ADX rats following GHS treatment was not due to increased fat mass or increased weight of other organs measured. Food intake was increased for up to 7 h following a single injection of GHRP-6 in both the adrenal-intact (P , 0.01) and corticosterone-replacement groups (P , 0.05). This stimulating effect on food intake was not observed at any time point in the ADX rats without corticosterone replacement. Conclusion: These data suggest that GHS-induced body weight gain is glucocorticoid-independent. However, basal levels of glucocorticoids are permissive for the GHS-induced increase in food intake whilst activation of the hypothalamo -pituitary-adrenal axis appears to contribute to the GHSinduced accumulation of fat mass. European Journal of Endocrinology 150 905-911

Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus

“…In rodents, ghrelin administration activates a variety of stress-related behavioral and neuroendocrine responses. The ghrelin-induced increase of plasma glucocorticoids levels likely helps to cope with stress since glucocorticoids – similarly to ghrelin— increase glycemia, stimulate adiposity and enhance motivated behaviors (Dallman, 2010; Tschop et al, 2000; Tung et al, 2004). Notably, ghrelin signaling seems to be required for full activation of the HPA axis under some stress conditions (Chuang et al, 2011; Spencer et al, 2012).…”

Circulating hormones and hypothalamic energy balance: regulatory gene expression in the Lou/C and Wistar rats

“…TSH and T4 levels were lower in the Lou/C rat, although T3 levels were not significantly different, indicating central hypothyroidism that would act to limit energy expenditure in response to low body weight and low serum leptin levels. Corticosterone is permissive for appetite stimulation and body fat accumulation, and the higher levels observed in the Wistar rat may stimulate adiposity via the actions of hormones such as ghrelin (Tung et al 2004). Thus, the lower levels of plasma corticosterone levels in the Lou/C may contribute to their lower levels of WAT.…”

Neural Substrates Underlying Interactions between Appetite Stress and Reward

“…Conversely, ghrelin, at concentrations within the normal physiological range, stimulates the HPA axis, increasing hypothalamic CRF mRNA expression and raising plasma corticosterone levels [42]. It has been suggested that glucocorticoids may have permissive effects for ghrelin’s orexigenic and fat-accumulating effects [43]. Anxiety and depression are often associated with stress.…”