Published online Aug 27, 2014. doi: 10.4254/wjh.v6.i8.570
Revised: April 29, 2014
Accepted: May 28, 2014
Published online: August 27, 2014
Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease (NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabetes, and hypertension have been found to be closely associated with the incidence of NAFLD. Evidence suggests that obesity and insulin resistance are the major factors that contribute to the development of NAFLD. In comparing the factors that contribute to the buildup of excess calories in obesity, an imbalance of energy homeostasis can be considered as the basis. Among the peripheral signals that are generated to regulate the uptake of food, signals from adipose tissue are of major relevance and involve the maintenance of energy homeostasis through processes such as lipogenesis, lipolysis, and oxidation of fatty acids. Advances in research on adipose tissue suggest an integral role played by adipokines in NAFLD. Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transforming growth factor-β, and interleukin-6, are implicated in NAFLD. Other adipokines, such as leptin and adiponectin and, to a lesser extent, resistin and retinol binding protein-4 are also involved. Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription factors, namely peroxisome proliferator-activated receptor (PPAR)-α. Recent studies have proposed downregulation of PPAR-α in cases of hepatic steatosis. This review discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD.
Core tip: Nonalcoholic fatty liver disease (NAFLD) is one of the principal causes for chronic liver disease. Recent reports suggested a positive association between cytokines secreted by the adipocytes, such as tumor necrosis factor-α, transforming growth factor-β, and interleukin (IL)-6 in NAFLD. Furthermore, hepatic natural killer T-cells produce IL-13 and IL-4; IL-13 may then activate hepatic stellate cells to produce pro-inflammatory cytokines and initiate oxidative stress, iron overload and fibrosis. Downregulation of peroxisome proliferator-activated receptors (PPAR), particularly PPAR-α in cases of hepatic steatosis, may facilitate the activity of hepatic proinflammatory cytokines. Hence, PPAR-γ and PPAR-α ligands have been considered for administration to prevent the initial inflammatory reactions and render protection to the liver cells.