Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, with a global prevalence estimated at approximately 25%. NAFLD is also the leading cause of liver cirrhosis, hepatocellular carcinoma, and death. Additionally, the risk of cardiovascular disease increases with greater NAFLD severity. The liver- and cardiovascular disease-related mortality incident rate ratios among the NAFLD population were 0.77 and 4.79 per 1,000 person-years, respectively. We intend to discuss the risk factors associated with NAFLD in terms of development and progression. Obesity or higher body mass index is closely associated with NAFLD in a dose-dependent manner, but growing evidence suggests that central obesity plays a more important role in the development of NAFLD. Saturated fat and fructose have been reported to be closely related to NAFLD. Fructose intake promotes lipogenesis and impairs mitochondria fat oxidation. The presence of type 2 diabetes is the most powerful predictive risk factor for hepatic fibrosis in patients with NAFLD. Single nucleotide polymorphism is not only associated with the prevalence of NAFLD but also associated with increased liver disease mortality. Obstructive sleep apnea, intestinal dysbiosis, and sarcopenia are associated with the development of NAFLD

AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models. METHODS: Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW. RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α. CONCLUSION: PPAR-δ agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.