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Do peroxisome proliferator-activated receptor targeted treatments have a role in fatty liver disease?

Non-alcoholic fatty liver disease (NAFLD) encompasses the spectrum of diseases ranging from pure steatosis (i.e. uncomplicated fatty liver) to non-alcoholic steatohepatitis (NASH), and ultimately cirrhosis. The optimal pharmacological treatment for people with NAFLD remains uncertain.
This timely review discusses the potential of novel therapies targeting peroxisome proliferator-activated receptors (PPARs) for modulation of NAFLD. Notably, PPAR-alpha is closely linked to the transcription of genes related to hepatic beta-oxidation, such as CPT-1 and is highly expressed in the liver. In experimental studies, activation of PPAR-alpha by fenofibrate markedly ameliorated hepatic insulin resistance due to upregulation of enzymes involved with beta-oxidation, and upregulation of genes involved in hepatic lipid oxidation, as well as inhibition of de novo lipogenesis and gluconeogenesis enzymes, resulting in a significant decrease in hepatic steatosis. Whether these experimental findings translate to the clinical setting merits further evaluation.
The role of peroxisome proliferator-activated receptor in the treatment of non-alcoholic fatty liver disease.

Sun X, Zhang Y, Xie M