J Lipid Atheroscler.  2017 Jun;6(1):1-7. 10.12997/jla.2017.6.1.1.

Bile Acid Receptor Farnesoid X Receptor: A Novel Therapeutic Target for Metabolic Diseases

• Fang S

• KMID: 2385838
• DOI: http://doi.org/10.12997/jla.2017.6.1.1

Abstract

Bile acid has been well known to serve as a hormone in regulating transcriptional activity of Farnesoid X receptor (FXR), an endogenous bile acid nuclear receptor. Moreover, bile acid regulates diverse biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism and energy expenditure. Alteration of bile acid metabolism has been revealed in type II diabetic (T2D) patients. FXR-mediated bile acid signaling has been reported to play key roles in improving metabolic parameters in vertical sleeve gastrectomy surgery, implying that FXR is an essential modulator in the metabolic homeostasis. Using a genetic mouse model, intestinal specific FXR-null mice have been reported to be resistant to diet-induced obesity and insulin resistance. Moreover, intestinal specific FXR agonism using gut-specific FXR synthetic agonist has been shown to enhance thermogenesis in brown adipose tissue and browning in white adipose tissue to increase energy expenditure, leading to reduced body weight gain and improved insulin resistance. Altogether, FXR is a potent therapeutic target for the treatment of metabolic diseases.

Keyword

Bile acids; Farnesoid X receptor; Metabolic diseases

MeSH Terms

Adipose Tissue, Brown
Adipose Tissue, White
Animals
Bile Acids and Salts
Bile*
Biological Processes
Body Weight
Energy Metabolism
Felodipine
Gastrectomy
Homeostasis
Humans
Insulin Resistance
Metabolic Diseases*
Metabolism
Mice
Obesity
Thermogenesis
Bile Acids and Salts
Felodipine

Figure

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  Fig. 1 Structure and transcriptional regulation of nuclear receptor. NR; nuclear receptor.

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  Fig. 2 Regulation of cholesterol/bile acid metabolism by FXR. CYP7A1; Cholesterol-7α-hydroxylase, SHP; Small heterodimer partner, RXR; Retinoid X receptor, FXR; Farnesoid X receptor.

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  Fig. 3 Regulation of bile acid synthesis by FXR in the intestine. FXR; Farnesoid X receptor, RXR; Retinoid X receptor, FGFR4; Fibroblast Growth Factor Receptor 4, CYP7A1; Cholesterol-7α-hydroxylase.

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  Fig. 4 Physiological regulation of whole body metabolism by FXR in the intestine. RXR; Retinoid X receptor, FXR; Farnesoid X receptor.

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