The liver is the central organ involved in lipid metabolism. Dyslipidemia and its related disorders, including non-alcoholic fatty liver disease(NAFLD), obesity and other metabolic diseases, are of increasing public h...The liver is the central organ involved in lipid metabolism. Dyslipidemia and its related disorders, including non-alcoholic fatty liver disease(NAFLD), obesity and other metabolic diseases, are of increasing public health concern due to their increasing prevalence in the population. Besides their well-characterized functions in cholesterol homoeostasis and nutrient absorption, bile acids are also important metabolic regulators and function as signaling hormones by activating specific nuclear receptors, G-protein coupled receptors, and multiple signaling pathways. Recent studies identified a new signaling pathway by which conjugated bile acids(CBA) activate the extracellular regulated protein kinases(ERK1/2) and protein kinase B(AKT) signaling pathway via sphingosine-1-phosphate receptor 2(S1PR2). CBA-induced activation of S1PR2 is a key regulator of sphingosine kinase 2(Sph K2) andhepatic gene expression. This review focuses on recent findings related to the role of bile acids/S1PR2-mediated signaling pathways in regulating hepatic lipid metabolism.展开更多
基金supported by A.D.Williams Award (to Huiping Zhou)National Institutes of Health (NIH,No.R01 DK-057543 to Phillip B.Hylemon and Huiping Zhou)+1 种基金supported by VA Merit Awards (No.1BX0013828-01 to Phillip B.HylemonNo.1I01BX001390 to Huiping Zhou)
文摘The liver is the central organ involved in lipid metabolism. Dyslipidemia and its related disorders, including non-alcoholic fatty liver disease(NAFLD), obesity and other metabolic diseases, are of increasing public health concern due to their increasing prevalence in the population. Besides their well-characterized functions in cholesterol homoeostasis and nutrient absorption, bile acids are also important metabolic regulators and function as signaling hormones by activating specific nuclear receptors, G-protein coupled receptors, and multiple signaling pathways. Recent studies identified a new signaling pathway by which conjugated bile acids(CBA) activate the extracellular regulated protein kinases(ERK1/2) and protein kinase B(AKT) signaling pathway via sphingosine-1-phosphate receptor 2(S1PR2). CBA-induced activation of S1PR2 is a key regulator of sphingosine kinase 2(Sph K2) andhepatic gene expression. This review focuses on recent findings related to the role of bile acids/S1PR2-mediated signaling pathways in regulating hepatic lipid metabolism.
