Adiponectin, a key adipokine in obesity related liver diseases

Abstract

Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis, non-alcoholic steatohepatitis (NASH), and progressive liver fibrosis is considered the most common liver disease in western countries. Fatty liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin resistance. Hepatic steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of patients. Besides liver biopsy no diagnostic tools to identify patients with NASH are available, and no effective treatment has been established. Visceral obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage, insulin resistance, and progressive liver damage. Most of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver damage. Adiponectin is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or NASH. Adiponectin antagonizes excess lipid storage in the liver and protects from inflammation and fibrosis. This review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin.

Keywords: Adiponectin; Adipose tissue; Hepatic steatosis; Non-alcoholic steatohepatitis; Obesity.

Figure 1

Crosstalk of visceral adipose tissue and the liver. Free fatty acids and Interleukin (IL)-6 released by visceral adipose tissue (VAT) are transported to the liver by the portal vein. Free fatty acids promote steatosis, enhance β-oxidation and the release of very low density lipoproteins (VLDL) contributing to dyslipidemia. IL-6 induces hepatic C-reactive protein (CRP) synthesis and suppressor of cytokine signalling 3 (SOCS3), and thereby is linked to systemic inflammation and hepatic insulin resistance, respectively (adapted from Schaffler A, Scholmerich J, Buchler C. Mechanisms of disease: adipocytokines and visceral adipose tissue--emerging role in nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2005; 2: 273-280[6]). ER: Endoplasmatic reticulum; TG: Triglycerides.

Figure 2

Epidemiology of non-alcoholic fatty liver disease. Current estimates of the prevalence of fatty liver, non-alcoholic steatohepatitis (NASH) and obesity-related liver cirrhosis in the general population and in obesity defined as body mass index (BMI) above 30 kg/m².

Figure 3

Hepatoprotective effects of adiponectin. Hepatic insulin resistance correlates with liver fat content, and is currently thought to represent the first incident in metabolic liver diseases. Insulin resistance and steatosis may also promote inflammation and fibrosis although the factors leading to advanced liver damage have not been identified so far. Major pathophysiological alterations of hepatocytes, hepatic stellate cells (HSC) and Kupffer cells in hepatic steatosis and/or non-alcoholic steatohepatitis are indicated. The protective activities of adiponectin are listed and arrows indicate an induction or repression of these pathways/proteins by adiponectin. IL: Interleukin; TGF: Transforming growth factor; TNF: Tumor necrosis factor; ECM: extracellular matrix; ROS: Reactive oxygen species.