%0 Journal Article
%T PPARs in Liver Diseases and Cancer: Epigenetic Regulation by MicroRNAs
%A Marion Peyrou
%A Pierluigi Ramadori
%A Lucie Bourgoin
%A Michelangelo Foti
%J PPAR Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/757803
%X Peroxisome-proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that exert in the liver a transcriptional activity regulating a whole spectrum of physiological functions, including cholesterol and bile acid homeostasis, lipid/glucose metabolism, inflammatory responses, regenerative mechanisms, and cell differentiation/proliferation. Dysregulations of the expression, or activity, of specific PPAR isoforms in the liver are therefore believed to represent critical mechanisms contributing to the development of hepatic metabolic diseases, disorders induced by hepatic viral infections, and hepatocellular adenoma and carcinoma. In this regard, specific PPAR agonists have proven to be useful to treat these metabolic diseases, but for cancer therapies, the use of PPAR agonists is still debated. Interestingly, in addition to previously described mechanisms regulating PPARs expression and activity, microRNAs are emerging as new important regulators of PPAR expression and activity in pathophysiological conditions and therefore may represent future therapeutic targets to treat hepatic metabolic disorders and cancers. Here, we reviewed the current knowledge about the general roles of the different PPAR isoforms in common chronic metabolic and infectious liver diseases, as well as in the development of hepatic cancers. Recent works highlighting the regulation of PPARs by microRNAs in both physiological and pathological situations with a focus on the liver are also discussed. 1. Introduction Obesity, the metabolic syndrome (MetS), diabetes, hepatitis viruses (HBV/HCV), and abusive alcohol consumption are currently the principal etiological factors favoring the occurrence of hepatocellular adenoma and carcinoma worldwide [1¨C8]. With obesity, MetS, and diabetes, the liver can develop a wide spectrum of disorders, occurring in individuals in absence of excessive alcohol consumption, or HBV/HCV infections, and ranging from insulin resistance (IR), nonalcoholic fatty liver diseases (NAFLD, including steatosis and insulin resistance), to nonalcoholic steatohepatitis (NASH, inflammation, and fibrosis associated with steatosis), and to cirrhosis (characterized by replacement of liver tissue by extracellular matrix and regenerative nodules) [9, 10]. Hepatocellular adenoma (HCA) and carcinoma (HCC) can then occur as the ultimate stage of these diseases [11¨C13]. Since obesity and metabolic diseases have reached pandemic proportions worldwide, the incidence of IR/NAFLD/NASH/cirrhosis and HCA/HCC is expected to dramatically increase in the future, likely
%U http://www.hindawi.com/journals/ppar/2012/757803/