Recent advances in regulating cholesterol and bile acid metabolism

ABSTRACT

Cholesterol is an important component of lipids in animal membranes. All living cells can synthesize cholesterol, but the amount of synthesis is not sufficient, and therefore cholesterol synthesized in the liver is delivered to extrahepatic tissues as a form of LDL. The liver is a primary organ to not only synthesize but also catabolize cholesterol into bile acids, which ends up to excrete with the feces. The synthetic and catabolic pathways are precisely regulated under the negative-feedback control system under the transcriptional regulation driven by several transcription factors such as the sterol regulatory element-binding proteins (SREBPs), the liver x receptor, and the farnesoid x receptor. This review summarizes various findings including our recent discoveries in the molecular mechanism of activation of SREBP that is involved in the regulation of hepatic cholesterol biosynthesis, and a novel function of the metabolic end product of cholesterol, bile acids, in skeletal muscles.

Cholesterol and its metabolites regulate the activity of SREBP, LXR, and FXR, thereby controlling their target gene expression. TGR5 activation triggers the downstream signal transduction.

KEYWORDS:

• Cholesterol
• bile acid
• SREBP
• INSIG
• TGR5

Acknowledgments

The author would like to thank Enago for the English language review.

Disclosure statement

No potential conflict of interest was reported by the author.

Additional information

Funding

This work was supported by the Japan Agency for Medical Research and Development [16gm0910008h0001]; Ministry of Education, Culture, Sports, Science and Technology [Grants-in-Aid for Scientific Research (S) 15H05781].