Peripheral leptin and ghrelin receptors are regulated in a tissue-specific manner in activity-based anorexia

The aim of this research was to investigate the effect of long-term exposure to low leptin and high ghrelin levels, inherent to activity-based anorexia (ABA), on peripheral metabolism-implicated tissues such as muscle and fat depots. For this purpose, rats under ABA were submitted to a global study which included the characterization of body weight and composition change, the evaluation of leptin and ghrelin levels as well as their receptors expression at peripheral level. Our results confirm that feeding restriction to 1 h per day, and particularly the combination of this fasting regime with exercise (ABA), significantly reduces fat mass, decreases leptin circulating levels, increases ghrelin levels strikingly and enhances insulin sensitivity. By direct in vitro assays, we show that visceral and gonadal fat participate more than subcutaneous fat in the hypoleptinemia of these animals. The study of ghrelin (GHS-R1a) and leptin (LEPR) receptors at peripheral level exhibits a tissue-specific expression pattern. Concretely, oxidative-soleus type of muscle appears to be more susceptible to ghrelin and leptin circulating levels than glycolytic-gastrocnemius type under exercise and food restriction situations. In relation to adipose tissue, chronic hyperghrelinemia induces GHS-R1a expression on visceral and subcutaneous fat which might suggest the prevention of lipid loss. On the other hand, only subcutaneous fat express the active long form of LEPR compared to visceral and gonadal fat under low leptin levels in ABA animals. All together, these findings indicate tissue-specific mechanisms for the control of energy homeostasis in response to nutrient and energy availability.