Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions

Abstract

Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD). Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC) also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

Hepatocyte-Macrophage Acetoacetate Shuttle Protects against Tissue Fibrosis

“…The likelihood that an AcAc shuttle's coordination of hepatic fibrogenesis signals first through lobular macrophages is supported by a lack of phenotype in adipose tissue of SCOT-Macrophage-KO mice. Thus, extrahepatic alteration of myeloid cells and/or secretion of adipokines are likely not significant contributors to hepatic fibrogenesis in the SCOT-Macrophage-KO mice model (Adolph et al, 2017). Finally, the presence of abundant desmin + /SCOT + cells in livers of fibrogenic SCOT-Macrophage-KO mice suggests that the effects of AcAc on these effector cells are first modulated through local LysM-Cre + cells.…”

Relationship between Heart Disease and Liver Disease: A Two-Way Street

“…In addition to the role of abdominal obesity, which usually occurs in NAFLD, ectopic fat accumulation in other districts (i.e. perivascular, pericardial, and epicardial) leads to adipocytes dysfunction with consequent imbalance of pro-and anti-inflammatory cytokinesoriginating from adipose tissue termed adipokines [101,102].In this context, an increase in proinflammatory cytokines such as leptin and a decrease of cardioprotective one such as adiponectin have been reported in NAFLD [102].This induces a persistent deterioration of the inflammatory and insulin resistant states that consequently lead to the worsening of cardiometabolic outcomes [101].…”

Effect of maternal high-fat diet on key components of the placental and hepatic endocannabinoid system

“…In our animal model (Papio spp. ), exposure of adult nonpregnant animals to 7-14 wk of a HFD was associated with hyperlipidemia and inflammation (48,72), which are features of the metabolic syndrome in humans that ultimately could lead to NAFLD (2). In general, in the human population, morbid obesity was associated with liver steatosis in 88% of the studied group, with an average age of 43.1 yr (73).…”