Functions of Ghrelin in Brain, Gut and Liver

Ghrelin production occurs in the gastrointestinal tract with the greatest concentration in the fundus of the stomach, which accounts for approximately 75-80% of circulating ghrelin levels. Desacyl ghrelin has been suggested to be involved in the regulation of energy homeostasis because of its ability to cross the blood-brain barrier and to induce increased neuronal activity in the hypothalamic arcuate nucleus. The enzyme called ghrelin O-acyl transferase is able to acylate ghrelin and regulates the physiological functions of the final peptide acyl ghrelin. The acylated ghrelin has an anti-inflammatory function that depends on its direct effect on T lymphocytes and monocytes, in which it inhibits the expression of proinflammatory cytokines such as Interleukin-1 beta (IL-1 beta), Interleukin-6 (IL-6), and Tumor Necrosis Factor (TNF-alpha). Some studies conducted in animal models show that ghrelin treatment reduces the amount of fibrogenic cells. In particular, ghrelin treatment decreases alpha -SMA protein expression, hepatic content of hydroxyproline and reduces the elevation of serum aspartate aminotransferase levels. Moreover, ghrelin attenuates liver injury and collagen deposition through inhibition of hepatic cell apoptosis and antioxidative activity, at least in part by nitric oxide induction. Several studies suggest that the orexigenic action of ghrelin is mediated via the neuropeptide Y neurons in the arcuate nucleus. Neuropeptide Y overexpression in the dorsomedial hypothalamus can cause hyperphagia and obesity in rat, which in turn causes liver steatosis, inflammation and fibrosis. The aims of this review were to examine and discuss the different functions of this hormone, particularly those that link the brain, gut and liver.