On the other hand, the exacerbated inflammatory response could just be secondary to increased hepatic lipid accumulation in ethanol-fed

lipin-1LKO mice. Up-regulation of hepatic proinflammatory cytokines and excess production of reactive oxygen species (ROS) in lipin-1LKO mice are likely to contribute to markedly elevated serum makers of liver injury. Additional studies evaluating the ability of lipin-1 to repress the activity of transcriptional factors such as NFATc4 or NF-κB and to attenuate the production of cytokines or ROS in response to LPS or ethanol in Kupffer cells are currently under investigation in our laboratory. The Lieber-DeCarli liquid diets enriched in polyunsaturated fat promotes ethanol-induced liver injury in rodents.[1] Our present study used a modified Lieber-DeCarli low-fat ethanol-containing liquid diet.[17] It MAPK inhibitor is possible that hepatic lipin-1 may be influenced by dietary fat and composition. We are currently investigating the effects of dietary fat and composition on ethanol-mediated impairments of lipin-1. The present study demonstrates that ethanol metabolism by

way of ADH and ALDH2 induces nucleocytoplasmic shuttling of lipin-1α, inhibiting PGC-1α activity and causing fat accumulation in cultured hepatocytes. These in vitro findings further support the notion that depletion of hepatic nuclear lipin-1 in lipin-1LKO mice may largely contribute to the drastic liver responsiveness to ethanol challenge. The role of hepatic ethanol metabolism-induced production of metabolites, redox see more state shift, or ROS in regulation

of lipin-1α nucleocytoplasmic shuttling merits investigation. In summary, using liver-specific lipin-1-null mice fed an ethanol-containing diet, we demonstrated for the first time that liver-specific deletion of lipin-1 leads to the rapid onset and progression of alcoholic steatohepatitis, providing novel insights into the biological click here function of lipin-1 in alcoholic steatohepatitis. Our present findings suggest that the development of nutritional or pharmacological agents to enhance nuclear lipin-1 activity could be a promising approach toward developing new options for the prevention and treatment of human alcoholic steatohepatitis. Additional Supporting Information may be found in the online version of this article. “
“Crohn’s disease (CD) is a multifactorial disorder with a pivotal role of the genetic component. A single nucleotide polymorphism in heat shock protein 70-2 (HSP70-2) has been shown to be associated with a severe clinical course in CD. The purpose of this study was to identify associations between the HSP70-2 polymorphism and the clinical courses of CD in the Chinese population. One hundred patients with CD and 190 healthy individuals were genotyped for the HSP70-2 PstI polymorphism by restriction fragment length polymorphism analysis. The genotype frequency of the PstI polymorphism did not differ between patients and controls.