The new mechanism of Ghrelin/GHSR-1a on autophagy regulation

Abstract Autophagy is associated with several diseases. In recent years, accumulating evidence has suggested that ghrelin pathway exerts a protective effect by regulating autophagy. This review aims to assess the potential role and use of ghrelin as a new treatment for obesity, cardiovascular diseases, nonalcoholic fatty liver disease (NFALD), neurodegenerative diseases, and tissue damage associated with autophagy. Ghrelin reduces the basal expression of autophagy-related genes in obesity-associated type 2 diabetes and ghrelin level changes in obesity, heart failure, and NFALD as well as altered autophagy. Ghrelin and its receptor GHSR-1 activation induce the phosphorylation of ERK1/2 and the induction of PI-3 kinase (PI3 K) and phosphorylation of Akt. In the myocardium and hypothalamic NPY/AgRP neurons, ghrelin increases levels of the intracellular energy sensor AMPK and enhances autophagy, protecting cardiac ischemia and inducing neural stem cells. Nonetheless, ghrelin activates the PI3 K/Akt/Bcl-2 pathway and inhibits the activation of autophagy, such as tissues injured by sepsis or doxorubicin. In conclusion, endogenous ghrelin system could be considered as a new target or treatment for metabolism disorders, cardiac diseases, neurodegenerative diseases, and tissue injuries.