Modulation of Cell Death and Survival by Adipokines in the Liver

Abstract

Adipokines, hormones predominantly produced from adipose tissue, have been shown to impart dynamic functions in the liver. Emerging evidence has shown that adipokines are also involved in modulating liver cell survival and/or death. Among the various adipokines, adiponectin and leptin directly regulate proliferation of hepatocytes, Kupffer cells, and hepatic stellate cells. Moreover, these adipokines control apoptosis and cell cycle of hepatic cancer cells in a complex manner. Adiponectin possesses both pro-and anti-proliferative properties, whereas leptin appears to play roles as a pro-survival hormone. Recent studies have revealed that regulation of cell death and proliferation is one of the critical factors regulating liver physiology by adipokines. In this review, we summarize the effects of adipokines on apoptosis and survival of liver cells and also demonstrate their implications in regulating various liver functions and decipher the underlying molecular mechanisms.

Adiponectin inhibits inflammatory cytokines production by Beclin‐1 phosphorylation and B‐cell lymphoma 2 mRNA destabilization: role for autophagy induction

“…Both DAPK1 activation and TTP induction are involved in autophagy activation via the modulation of Beclin-1 and Bcl-2 protein interaction, which inhibits LPS-primed inflammatory cytokines expression regulation of autophagy induction, and inhibition of such an interaction is a plausible mechanism for the initiation of autophagy. Emerging evidence suggests that autophagy induction plays a crucial role in mediating many physiological responses induced by adiponectin (Nepal and Park, 2015). However, its underlying molecular mechanisms are not clearly understood.…”

Plasma Adiponectin and Hepatocellular Carcinoma Survival Among Patients Without Liver Transplantation

“…Ectopic overexpression of adiponectin increased proliferation, invasion, as well as the expression of downstream genes (cyclin D1 and β-catenin) in Hep3B and HepG2 cells (16). However, adiponectin also showed dual molecular functions of anti-inflammatory, pro-inflammatory, anti-apoptotic and apoptosis induction effects (25, 26). A deeper exploration of the functional networks in hepatocarcinogenesis and progression can help to further understand the complex role of adiponectin as a tumor suppressor or promoter.…”

Adipokines in Liver Cirrhosis

“…These cells become activated upon liver injury and start to proliferate and produce extracellular matrix proteins. Adiponectin reduces hepatic stellate cell activation, proliferation and survival [ 43 , 44 ]. Connective tissue growth factor is one of the profibrotic cytokines released by hepatocytes and is reduced by adiponectin [ 45 ].…”

“…Various review articles have been published summarizing the inflammatory and profibrogenic effects of leptin in the liver [ 44 , 46 , 110 ]. Therefore, these issues are not further addressed herein.…”