Physiological role of 16a- hydroxylated bile acid in energy intake and hepatic lipid metabolism.

PROJECT SUMMARY/ABSTRACT Bile acids are regulatory molecules in energy intake and lipid metabolism. Controlling energy intake and lipid metabolism are essential for human health, and these modifications can prevent obesity and obesity-induced metabolic diseases. Structural differences, especially the hydroxyl group position of bile acid, are crucial factors in determining the effect of bile acid on metabolism. We have found that the 16α hydroxylation at bile acid enhances the production of bioactive lipids involving energy intake and hepatic lipid metabolism in mice. However, the beneficial effect of 16α hydroxylated bile acid in mammalian metabolism has not been investigated because the 16α- hydroxylation at bile acid is not seen in mammals. In this grant, we propose to determine the physiological role of 16α-hydroxylated bile acid in metabolism and underlying biology. How does 16α-hydroxylated bile acid regulate energy intake and lipid metabolism? How does 16α- hydroxylated bile acid enhance bioactive lipids synthesis? We will use primary hepatocytes and intestinal organoids culture, Seahorse for evaluation of mitochondrial function, reporter assay for mechanism study, and tissue-specific knockout mice in this proposal. The success of this work is expected to elucidate the specific targeting site of bile acid for the regulation of energy intake and lipid metabolism.