Title:Functions of Ghrelin in Brain, Gut and Liver
VOLUME: 15 ISSUE: 8
Author(s):Cristina Stasi and Stefano Milani
Affiliation:Department of Experimental and Clinical Medicine, University of Firenze - School of Medicine, Azienda Ospedaliero Universitaria Careggi - AOUC, Largo Brambilla, 3 I-50134 - Firenze Italy.
Keywords:Brain, fibrosis, ghrelin, gut, liver, neuropeptide Y.
Abstract: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-1β (IL-1β), Interleukin-6 (IL-6), and Tumor Necrosis Factor (TNF-α).
Some studies conducted in animal models show that ghrelin treatment reduces the amount of fibrogenic
cells. In particular, ghrelin treatment decreases α -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.
