Bile Acids as Metabolic Inducers of Hepatocyte Proliferation and Liver Regeneration

Liver regeneration is an orchestrated process that mainly comprises of the proliferation of the major liver cell types, that is, the hepatocytes and cholangiocytes, after liver injury (physical or chemical) in vivo. Although having a remarkable capacity to regenerate in vivo, hepatocytes are difficult to grow and maintain in culture as their viability and functions decline with time. The lack of a sufficient source of viable hepatocytes limits their clinical use for therapeutic applications. In the current review, we have summarized the role of bile acids and their subsequent signaling pathways in liver regeneration in terms of both hepatocyte and cholangiocyte proliferation. We have also reviewed bile acid–based therapies in liver diseases. The expression of two major bile acid receptors, the farnesoid X receptor (FXR) and the Takeda G protein–coupled receptor (TGR5) in both the liver and the intestine immensely contribute to hepatocyte proliferation through varied mechanisms. Selective potent agonists of these two pathways are being synthesized for use as new therapies in several liver diseases. FXR/TGR5 agonists hold immense potential to facilitate liver regeneration and ameliorate hepatic insufficiency in chronic liver diseases.