Scientific publications

Molecular and cellular mechanisms underlying the hepatoprotective role of ghrelin against NAFLD progression

Nov 22, 2022 | Magazine: Journal of Physiology and Biochemistry

Carlota Tuero  1 , Sara Becerril  2   3   4 , Silvia Ezquerro  2 , Gabriela Neira  2 , Gema Frühbeck  2   3   4   5 , Amaia Rodríguez  6   7   8


The underlying mechanisms for the development and progression of nonalcoholic fatty liver disease (NAFLD) are complex and multifactorial. Within the last years, experimental and clinical evidences support the role of ghrelin in the development of NAFLD. Ghrelin is a gut hormone that plays a major role in the short-term regulation of appetite and long-term regulation of adiposity.

The liver constitutes a target for ghrelin, where this gut-derived peptide triggers intracellular pathways regulating lipid metabolism, inflammation, and fibrosis. Interestingly, circulating ghrelin levels are altered in patients with metabolic diseases, such as obesity, type 2 diabetes, and metabolic syndrome, which, in turn, are well-known risk factors for the pathogenesis of NAFLD.

This review summarizes the molecular and cellular mechanisms involved in the hepatoprotective action of ghrelin, including the reduction of hepatocyte lipotoxicity via autophagy and fatty acid β-oxidation, mitochondrial dysfunction, endoplasmic reticulum stress and programmed cell death, the reversibility of the proinflammatory phenotype in Kupffer cells, and the inactivation of hepatic stellate cells.

Together, the metabolic and inflammatory pathways regulated by ghrelin in the liver support its potential as a therapeutic target to prevent NAFLD in patients with metabolic disorders.

CITATION  J Physiol Biochem. 2022 Nov 22. doi: 10.1007/s13105-022-00933-1