Ghrelin and Leptin in Fasting

Animals and humans when exposed to conditions of energy deficit make compensatory changes in the efficiency of energy utilization and activity to conserve energy for essential functions, thereby maintaining homeostasis. The decrease in whole body energy expenditure stems from changes in metabolism at the cellular level. Cellular metabolism is modified in response to activation of neural and hormonal regulatory systems, such as down-regulation of sympathetic outflow to major organs, e.g. heart, increased sympathetic outflow to white adipose tissue (to mobilize lipids) and changes in secretion of ghrelin and leptin [1]. Ghrelin is an appetite-stimulating peptide secreted mainly by the stomach and acts as a ligand for the growth hormone (GH) secretagogue receptor [2]. Ghrelin is secreted in a pulsatile manner, peaking at 2000 h, rising before meals and returning to baseline levels after food ingestion. Since ghrelin discovery in 1999, it has been studied as a potential anti-obesity therapeutic target because central and peripheral ghrelin administration increases appetite and promotes food intake in rodents and humans and, in long run, induces adiposity in rodents [3]. This implies its importance in feeding behaviour and provides a link between the stomach and brain in the regulation of energy homeostasis. Acylated ghrelin, having an n-octanoyl moiety attached to the serine at position 3, is the most active form of ghrelin and accounts for only 5%–10% of the total circulating ghrelin. The enzyme responsible for ghrelin acylation has been recently discovered. The enzyme, ghrelin-O-acyltransferase (GOAT) is a member of the membrane-bound acyltransferase family of proteins, and information regarding the regulation of its expression is limited. Acylated ghrelin stimulates food intake and induces weight gain [4]. In addition to the orexigenic effects of ghrelin, several other potential functions of ghrelin have been recently elucidated, including its role in gastrointestinal motility, gastric acid secretion and various cardiovascular, immunological, reproductive and behavioural processes [5]. Leptin is a satiety hormone, secreted in proportion to adipose tissue, informing the hypothalamus of the status of energy stores [6]. Leptin plays a crucial role in body weight homeostasis by regulating food intake and energy expenditure. Leptin receptors are expressed in several areas of the brain and mediate the central actions of leptin. High leptin levels signal the presence of sufficient energy stores to certain sites in the central nervous system, which respond by reducing appetite and increasing energy expenditure to prevent obesity [7]. In addition, leptin can promptly signal the shift …