Analysis of Liver Function in Retinoic Acid Receptor Gamma Liver Specific Knockout Mice

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) affects about one-third of the United States population and continues to grow in prevalence. Characterizing a spectrum of disease, NAFLD can range from simple steatosis to fibrosis and cirrhosis, which later can progress to hepatocellular carcinoma. Treatment options for this disease are currently limited to changing diet and exercise. Research efforts have been geared towards identifying and investigating potential targets for treatment of those with NAFLD. Via binding to retinoic acid, the biologically active metabolite of the micronutrient vitamin A (retinol), retinoic acid receptors (RARs α, β. γ) are known to regulate energy metabolism, and it has been shown that NAFLD leads to an altered/impaired state of vitamin A metabolism in the liver. In addition, our laboratory demonstrated that stimulation of the RA signaling pathway reduced hepatic steatosis in a High Fat Diet-induced NAFLD mouse model. Since RARγ is highly expressed in the liver, we are investigating the role of RARγ in NAFLD by characterizing the functional and molecular phenotypes of a murine liver-specific RARγ knockout. To date we have found that there is no difference in the vitamin A levels in the livers of these RARγ knockout mice. Through the characterization of this murine transgenic model, we will be able to determine the role of RARy in the liver, as well as to test new therapeutics that act via this receptor to potentially prevent/treat NAFLD.