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Nuclear Receptors in Nonalcoholic Fatty Liver Disease

DOI: 10.1155/2012/139875

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Abstract:

Nuclear receptors comprise a superfamily of ligand-activated transcription factors that are involved in important aspects of hepatic physiology and pathophysiology. There are about 48 nuclear receptors in the human. These nuclear receptors are regulators of many hepatic processes including hepatic lipid and glucose metabolism, bile acid homeostasis, drug detoxification, inflammation, regeneration, fibrosis, and tumor formation. Some of these receptors are sensitive to the levels of molecules that control lipid metabolism including fatty acids, oxysterols, and lipophilic molecules. These receptors direct such molecules to the transcriptional networks and may play roles in the pathogenesis and treatment of nonalcoholic fatty liver disease. Understanding the mechanisms underlying the involvement of nuclear receptors in the pathogenesis of nonalcoholic fatty liver disease may offer targets for the development of new treatments for this liver disease. 1. Introduction Liver diseases are a serious problem throughout the world. In Mexico, since 2000, cirrhosis and other chronic liver diseases have become among the main causes of mortality [1]. The incidence and prevalence of liver diseases are increasing along with changes in lifestyle and population aging, and these diseases were responsible for 20,941 deaths in 2007 [2]. In Mexico, the incidence of metabolic syndrome is also increasing. The metabolic syndrome has recently been associated with nonalcoholic fatty liver disease (NAFLD), and about 90% of patients with NAFLD have more than one feature of the metabolic syndrome [3]. The severity of NAFLD is one factor contributing to the development of nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma [4, 5]. The growing obesity epidemic requires a better understanding of the genetic networks and signal transduction pathways that regulate the pathogenesis of these conditions. A clear definition of the mechanisms responsible for metabolic control may provide new knowledge for the development of new drugs, with novel mechanisms of action, for the treatment of chronic liver diseases. The ability of individual nuclear receptors (NRs) to regulate multiple genetic networks in different tissues and their own ligands may represent a new class of potential drugs targets. To elucidate the challenges involved in developing such drugs, this paper focuses on the role of hepatic NRs in lipid metabolism and the possible effects on the physiopathology of NAFLD. 2. Nonalcoholic Fatty Liver Disease NAFLD is defined by the accumulation of triglycerides in

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