A role of peroxisome proliferator-activated receptor γ in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease is becoming a major health burden, as prevalence increases and there are no approved treatment options. Thiazolidinediones target the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) and have been investigated in several clinical trials for their potential in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). PPAR gamma has specialized roles in distinct tissues and cell types, and although the primary function of PPAR gamma is in adipose tissue, where the highest expression levels are observed, hepatic expression levels of PPAR gamma are significantly increased in patients with NAFLD. Thus, NAFLD patients receiving treatment with PPAR gamma agonists might have a liver response apart from the one in adipose tissue. Owing to the different roles of PPAR gamma, new treatment strategies include development of compounds harnessing the beneficial effects of PPAR gamma while restricting PPAR gamma unwanted effects such as adipogenesis resulting in weight gain. Furthermore, dual or pan agonists targeting two or more of the PPARs have shown promising results in pre-clinical research and some are currently proceeding to clinical trials. This MiniReview explores adipose- and liver-specific actions of PPAR gamma, and how this knowledge may contribute in the search for new treatment modalities in NAFLD/NASH.