Adipocytokines and liver disease

Abstract

Adipose tissue is a massive source of bioactive substances known as adipocytokines, including tumor necrosis factor (TNF)-alpha, resistin, leptin, and adiponectin. Recent advances in medical research view obesity as a chronic low-grade inflammatory state. Hypertrophied adipocytes in obesity release chemokines that induce macrophage accumulation in adipose tissue. Accumulated macrophages in obese adipose tissue produce proinflammatory cytokines and nitric oxide, and these inflammatory changes induce adipocytokine dysregulation. The latter is characterized by a decrease in insulinsensitizing and anti-inflammatory adipocytokines, and an increase in proinflammatory adipocytokines. Adipocytokine dysregulation induces obesity-related metabolic disorders, the so-called metabolic syndrome. Metabolic syndrome is a cluster of metabolic abnormalities, including diabetes mellitus, hypertension, hyperlipidemia, and nonalcoholic steatohepatitis (NASH). Recent studies have revealed that obesity is an independent risk factor for chronic liver diseases, such as NASH, alcoholic liver disease, chronic hepatitis C, and hepatocellular carcinoma. A common mechanism underlying these hepatic clinical states is thought to be adipocytokine dysregulation. In this review, we discuss the association of adipocytokines, especially leptin, adiponectin, TNF-alpha, and resistin, with liver diseases.

Adiponectin upregulates hepatocyte CMKLR1 which is reduced in human fatty liver

“…Of note upregulation of CMKLR1 by adiponectin is already observed in vitro using purified human hepatocytes. Systemic adiponectin is reduced in patients with hepatic steatosis and NASH and may contribute to lower CMKLR1 protein in the liver of these patients (Kamada et al, 2008;Polyzos et al, 2010;Schaffler et al, 2005). Impaired hepatic adiponectin activity has been described in mice fed a MCD diet (Larter et al, 2008;Tomita et al, 2008) where systemic adiponectin is significantly higher because of lower body weight.…”

Hepatic FDG Uptake is not Associated with Hepatic Steatosis but with Visceral Fat Volume in Cancer Screening

“…Visceral fat accumulation has been known to play a role in steatosis and fibrosis in the pathogenesis and prognosis of nonalcoholic fatty liver disease [13]. Visceral obesity induces a chronic low-grade inflammatory state, because chemokines released by hypertrophied adipocytes induce macrophage accumulation in visceral fat tissue [14]. Infiltrated macrophages produce pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, macrophage chemoattractant protein-1, resistin and leptin) and nitric oxide, and these inflammatory changes induce adipokines dysregulation [14,15].…”

“…Visceral obesity induces a chronic low-grade inflammatory state, because chemokines released by hypertrophied adipocytes induce macrophage accumulation in visceral fat tissue [14]. Infiltrated macrophages produce pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, macrophage chemoattractant protein-1, resistin and leptin) and nitric oxide, and these inflammatory changes induce adipokines dysregulation [14,15]. Altered long-term expression of liver metabolic enzymes may be critical in the transition to the chronic inflammatory state [16].…”

Plasma Levels of Adiponectin and Primary Liver Cancer Risk in Middle-Aged Japanese Adults with Hepatitis Virus Infection: A Nested Case–Control Study

“…Adiponectin is a physiologically active polypeptide secreted by adipose tissues and its circulating levels are inversely associated with obesity (9). Earlier experimental studies suggested that adiponectin played a protective role in carcinogenesis via insulin sensitization, antiproliferation, anti-inflammation, and angiogenesis regulation (10), and data supported epidemiologic evidence that adiponectin levels were inversely associated with the risk of obesityrelated malignancies, such as breast, colorectal, endometrium, and prostate cancers (10).…”