Oxysterols and Bile Acid Act as Signaling Molecules That Regulate Cholesterol Homeostasis: Nuclear Receptors LXR, FXR, and Fibroblast Growth Factor 15/19

Intricate homeostatic mechanisms in animals enable the metabolic flexibility to maintain stable levels of nutrients despite constant fluctuation in their availability. At the cellular level, metabolites themselves can serve as indicators of metabolic status. Oxysterols and bile acids, first considered merely as the intermediates and the end products of steroidogenesis and cholesterol catabolism, are now well-recognized signaling molecules that regulate the cholesterol and bile acid homeostasis and integrate it with the other physiological processes. They do that primarily by binding to nuclear receptors: liver X receptors (LXRs) and farnesoid X receptor (FXR). Through LXR and FXR, oxysterols and bile acids maintain balanced, finely tuned regulation of the cholesterol and bile acid homeostasis integrated with the fatty acid and glucose metabolism. Furthermore, oxysterol-LXR and BA-FXR-FGF15/19 regulated pathways offer exciting opportunities for treating metabolic diseases and related disorders. In this chapter, I will review our current understanding of the metabolic pathways leading to oxysterols and bile acids and functions of oxysterols and bile acids that are mediated by nuclear receptors LXR and FXR.