Peroxisome proliferator-activated receptor α, a potential therapeutic target for alcoholic liver disease

Abstract

Alcoholic liver injury represents a progressive process with a range of consequences including hepatic steatosis, steatohepatitis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. Targeting key molecular regulators involved in the development of alcoholic liver injury may be of great value in the prevention of liver injury. Peroxisome proliferator-activated receptor α (PPARα) plays a pivotal role in modulation of hepatic lipid metabolism, oxidative stress, inflammatory response and fibrogenesis. As such, PPARα may be a potential therapeutic target for the treatment of alcoholic liver disease.

Keywords: Alcoholic liver disease; Fibrosis; Inflammation; Oxidative stress; Peroxisome proliferator-activated receptor α.

Figure 1

Protective role and partial mechanism of peroxisome proliferator-activated receptor α in alcoholic liver disease. Peroxisome proliferator-activated receptor α (PPARα) plays a critical role in modulation of hepatic lipid metabolism, oxidative stress, inflammatory response and fibrogenesis in alcoholic liver disease. Up-regulation of PPARα by its agonists (e.g., fibrates, WY14643) leads to increased expression of fatty acid oxidation and transport enzymes, alleviated oxidative stress by increasing the expression of genes involved in antioxidant enzymes (e.g., SOD and CAT), inhibited through activating nuclear factor kappa B (NF-κB) signal pathway and decreased fibrogenesis factors (e.g., TGF-β1 and HSC activation). SOD: Superoxide dismutase; CAT: Catalase; TGF-β1: Transforming growth factor beta 1; HSCs: Hepatic stellate cells; COX-2: Cyclooxygenase-2; HO-1: Heme oxygenase-1; TNFα: Tumor necrosis factor α; OPN: Osteopontin.