%0 Journal Article
%T Targeting Hepatic Glycerolipid Synthesis and Turnover to Treat Fatty Liver Disease
%A George G. Schweitzer
%A Brian N. Finck
%J Advances in Hepatology
%D 2014
%R 10.1155/2014/498369
%X Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of metabolic abnormalities ranging from simple hepatic steatosis (accumulation of neutral lipid) to development of steatotic lesions, steatohepatitis, and cirrhosis. NAFLD is extremely prevalent in obese individuals and with the epidemic of obesity; nonalcoholic steatohepatitis (NASH) has become the most common cause of liver disease in the developed world. NASH is rapidly emerging as a prominent cause of liver failure and transplantation. Moreover, hepatic steatosis is tightly linked to risk of developing insulin resistance, diabetes, and cardiovascular disease. Abnormalities in hepatic lipid metabolism are part and parcel of the development of NAFLD and human genetic studies and work conducted in experimentally tractable systems have identified a number of enzymes involved in fat synthesis and degradation that are linked to NAFLD susceptibility as well as progression to NASH. The goal of this review is to summarize the current state of our knowledge on these pathways and focus on how they contribute to etiology of NAFLD and related metabolic diseases. 1. Introduction Overwhelming evidence links obesity with increased risk for several chronic diseases including insulin resistance, diabetes mellitus, dyslipidemias, and nonalcoholic fatty liver disease (NAFLD). The condition, NAFLD, encompasses both hepatic steatosis (the accumulation of neutral lipid within the cytosol of hepatocytes) and the more severe nonalcoholic steatohepatitis (NASH; hepatic inflammation and fibrosis associated with steatotic lesions). With the epidemic of obesity in the USA, the occurrence of NAFLD has risen exuberantly, becoming the most common cause of liver disease [1, 2]. It is now estimated that 14¨C24% of the general population and up to 80% of morbidly obese subjects have contracted NAFLD [3¨C6]. Although hepatic steatosis is extremely prevalent, only a subset of afflicted individuals experience severe liver damage and progress to cirrhosis. Hepatic steatosis promotes an inflammatory state including augmented production of reactive oxygen species (ROS) and proinflammatory cytokines. This Ħ°second hitĦħ is believed to be required to drive the transition from simple steatosis to steatohepatitis [5, 7¨C9]. Although the exact cause of the inflammation is difficult to pinpoint, hepatic steatosis is linked to heightened production of ROS [7, 10¨C13], which are known to cause mitochondrial damage. Mitochondrial injury further exacerbates ROS production, diminishes the capacity to oxidize excess fatty acids, and is also
%U http://www.hindawi.com/journals/ahe/2014/498369/