Conclusion: Our findings provide new insight into the function of specific miRNAs in stem cell-derived MVs regulating HHSC activation and transdifferentiation, and their therapeutic potentials in alcohol induced liver injury and fibrosis. Disclosures: Hidekazu īsukamoto Dabrafenib in vitro – Consulting: Shionogi & Co., S. P. Pharmaceutics; Grant/Research Support: The Toray Co. The following people have nothing
to disclose: Phillip Levine, Kelly McDaniel, Shannon S. Glaser, Heather L. Francis, Yuyan Han, Julie Venter, Taylor Francis, Chang-Gong Liu, Gianfranco Alpini, Fanyin Meng Deranged adipocyte-derived adiponectin signaling contributes to the development of alcoholic liver disease and provides a mechanistic basis for interorgan crosstalk in the pathogenesis of this disease. Lipin-1 is an intracellular protein that exhibits dual functions
as a phosphatidic acid phosphohydrolase (PAP) and a transcriptional co-activator. Lipin-1 is highly expressed in adipocytes, and plays a vital role in the regulation of adipocyte development and function. Our group previously demonstrated that ethanol-mediated inhibition of adipose lipin-1 gene expression is closely correlated with development of alcoholic fatty liver in mice. In the present study, utilizing an adipocyte specific 丨ipin-1-deficient buy Metformin (Adn-lipin-1KO)mouse model, we aimed to examine the functional role of adipocyte lipin-1 in the development of alcoholic fatty liver in mice and investigated the underlying Tideglusib molecular mechanisms. We induced alcoholic fatty liver injury in male Adn-lipin-1 K〇 mice and their littermate (WT) controls, by placing them on Lieber-DeCarli ethanol-containing diet for 10 days and then administering a single dose of ethanol (5 g/kg body weight) via gavage. Removal of adipocyte lipin-1 in mice significantly increased
hepatic triglyceride and cholesterol accumulation compared to WT controls after ethanol feeding, and augmented elevation of serum AST and ALT concentrations. More importantly, loss of adipocyte lipin-1 exacerbated the development of ethanol-induced fatty liver injury. Further mechanistic studies demonstrated that the mRNA expression levels of adipocyte adiponectin as well as hepatic adiponectin receptor 1 and 2 were all drastically reduced in the Adn-lipin-1K〇 mice fed with either a control diet or an ethanol-containing diet compared to WT control mice, indicating an essential role of adipocyte lipin-1 in regulating adiponectin signaling. Chronically ethanol-fed Adn-lipin-1K〇 mice also showed substantial lower serum protein levels of total or HMW adiponectin accompanied by significantly reduced rates of hepatic fatty acid oxidation.
No related posts.