Our understanding of bile acid physiology including synthesis, interplay with metabolism, hepatic and enteric pathobiology, and utility in diagnostic testing has undergone a renaissance since recognition that bile acids are natural ligands for the intracellular nuclear farnesoid receptor (FXR, bile acid receptor NR1H4 restricted to cells involved with bile acid enterohepatic cycling) and the cell surface receptor TGR5 (G protein coupled bile acid receptor - located in enterocytes, Kupffer cells, sinusoidal endothelium, cholangiocytes, and tissues not participating in the enterohepatic circulation). For more than 5 decades, bile acids have been of interest to gastroenterologists and hepatologists in regard to their physiologic role in fat digestion/assimilation and pathology associated with cholestatic liver injury. There is escalating interest in the signaling capacity of bile acids as emerging disease mechanisms that are likely exploitable therapeutically for disease intervention. Of course of interest to me are emerging strategies for management of liver disease - but the spectrum of potential applications is far wider, impacting numerous pathologic processes external to the liver including the metabolic syndrome NASH/NAFLD so common in humans and in disorders involving the alimentary canal. That TGR5 cell receptor is widely expressed beyond tissues/cells involved with classic bile acid cycling, may add to the growing armamentarium of therapeutic targets applicable to diverse tissues and disease processes. This introductory discussion will lay the foundation for following lectures that will more discretely address emerging roles of bile acids in disease pathobiology.
展开▼
