![]() 5, 6 Large randomized controlled clinical trials have reported that both rosiglitazone and pioglitazone improve NAFLD-related hepatic steatosis and, in the case of pioglitazone, also hepatic inflammation and to a lesser extent fibrosis (Table 1). rosiglitazone and pioglitazone) have been the subject of increasing attention. In the quest of discovering relevant treatment targets, peroxisome proliferator-activated receptor γ (PPARγ) and the synthetic PPARγ agonists thiazolidinediones (TZD e.g. Although NAFLD and NASH represent a major burden to the patient and the supporting health system, there is currently no approved pharmacotherapy targeting the disease, emphasizing the current need for novel intervention strategies. 2, 3 The term NAFLD covers a wide range of hepatic disease states ranging from bland steatosis to non-alcoholic steatohepatitis (NASH) with developing hepatic fibrosis, which may progress and ultimately lead to cirrhosis and increased risk of hepatocellular carcinoma 2, 4. 2 NAFLD is closely linked to diet-induced dyslipidaemia, metabolic co-morbidities such as dysregulated glucose and lipid metabolism in turn promoting obesity, type 2 diabetes and cardiovascular diseases. 1 The increasing disease frequency reflects the high energy intake and sedentary lifestyle characteristics of modern day living, fuelling a cluster of detrimental lifestyle-associated diseases including NAFLD. The global prevalence of non-alcoholic fatty liver disease (NAFLD) has reached 25% of the adult population and continues to rise. This MiniReview explores adipose- and liver-specific actions of PPARγ, and how this knowledge may contribute in the search for new treatment modalities in NAFLD/NASH. 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. Owing to the different roles of PPARγ, new treatment strategies include development of compounds harnessing the beneficial effects of PPARγ while restricting PPARγ unwanted effects such as adipogenesis resulting in weight gain. Thus, NAFLD patients receiving treatment with PPARγ agonists might have a liver response apart from the one in adipose tissue. PPARγ has specialized roles in distinct tissues and cell types, and although the primary function of PPARγ is in adipose tissue, where the highest expression levels are observed, hepatic expression levels of PPARγ are significantly increased in patients with NAFLD. Thiazolidinediones target the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and have been investigated in several clinical trials for their potential in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Non-alcoholic fatty liver disease is becoming a major health burden, as prevalence increases and there are no approved treatment options.
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