Ghrelin-ghrelin O-acyltransferase system in the pathogenesis of nonalcoholic fatty liver disease

World J Gastroenterol. 2015 Mar 21;21(11):3214-22. doi: 10.3748/wjg.v21.i11.3214.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is currently considered as the most common liver disease in Western countries, and is rapidly becoming a serious threat to public health worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. The ghrelin-ghrelin O-acyltransferase (GOAT) system has recently been found to play a crucial role in both the development of steatosis and its progression to nonalcoholic steatohepatitis. Ghrelin, the natural ligand of the growth hormone secretagogue receptor, is a 28-amino acid peptide possessing a unique acylation on the serine in position 3 catalyzed by GOAT. The ghrelin-GOAT system is involved in insulin resistance, lipid metabolism dysfunction, and inflammation, all of which play important roles in the pathogenesis of NAFLD. A better understanding of ghrelin-GOAT system biology led to the identification of its potential roles in NAFLD. Molecular targets modulating ghrelin-GOAT levels and the biologic effects are being studied, which provide a new insight into the pathogenesis of NAFLD. This review probes into the possible relationship between the ghrelin-GOAT system and NAFLD, and considers the potential mechanisms by which the ghrelin-GOAT system brings about insulin resistance and other aspects concerning NAFLD.

Keywords: Energy homeostasis; Ghrelin-ghrelin O-acyltransferase system; Insulin resistance; Lipid metabolism; Nonalcoholic fatty liver disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acyltransferases / metabolism*
  • Animals
  • Energy Metabolism
  • Ghrelin / metabolism*
  • Humans
  • Insulin Resistance
  • Lipid Metabolism
  • Liver / enzymology*
  • Liver / pathology
  • Non-alcoholic Fatty Liver Disease / enzymology*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Prognosis
  • Receptors, Ghrelin / metabolism
  • Risk Factors
  • Signal Transduction*

Substances

  • Ghrelin
  • Receptors, Ghrelin
  • Acyltransferases
  • MBOAT4 protein, human