Therapeutic modulation of the bile acid pool by cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice

Chevre R, Trigueros-Motos L, Castano D, Chua T, Corliano M, Patankar J, Sng L, Sim L, Juin TL, Carissimo G, Ng LFP, Yi CNJ, Eliathamby CC, Groen AK, Hayden MR, Singaraja RR (2018)

Publication Type: Journal article

Publication year: 2018

Journal

The FASEB Journal Federation of American Society of Experimental Biology (FASEB)

Book Volume: 32

Pages Range: 3792-3802

Journal Issue: 7

DOI: 10.1096/fj.201701084RR

Abstract

Bile acids (BAs) are surfactant molecules that regulate the intestinal absorption of lipids. Thus, the modulation of BAs represents a potential therapy for nonalcoholic fatty liver disease (NAFLD), which is characterized by hepatic accumulation of fat and is a major cause of liver disease worldwide. Cyp8b1 is a critical modulator of the hydrophobicity index of the BA pool. As a therapeutic proof of concept, we aimed to determine the impact of Cyp8b1 inhibition in vivo on BA pool composition and as protection against NAFLD. Inhibition of Cyp8b1 expression in mice led to a remodeling of the BA pool, which altered its signaling properties and decreased intestinal fat absorption. In a model of cholesterol-induced NAFLD, Cyp8b1 knockdown significantly decreased steatosis and hepatic lipid content, which has been associated with an increase in fecal lipid and BA excretion. Moreover, inhibition of Cyp8b1 not only decreased hepatic lipid accumulation, but also resulted in the clearance of previously accumulated hepatic cholesterol, which led to a regression in hepatic steatosis. Taken together, our data demonstrate that Cyp8b1 inhibition is a viable therapeutic target of crucial interest for metabolic diseases, such as NAFLD.—Chevre, R., Trigueros-Motos, L., Castaño, D., Chua, T., Corlianò, M., Patankar, J. V., Sng, L., Sim, L., Juin, T. L., Carissimo, G., Ng, L. F. P., Yi, C. N. J., Eliathamby, C. C., Groen, A. K., Hayden, M. R., Singaraja, R. R. Therapeutic modulation of the bile acid pool by Cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice.

Authors with CRIS profile

Jay Patankar Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

ZKF-J68 (M1): Role of the transcription factor GATA4 in intestinal wound healing, inflammation, and cancer Oct. 1, 2017 - March 31, 2020

Involved external institutions

Agency for Science, Technology and Research (A*STAR) SG Singapore (SG) University of Groningen / Rijksuniversiteit Groningen NL Netherlands (NL)

How to cite

APA:

Chevre, R., Trigueros-Motos, L., Castano, D., Chua, T., Corliano, M., Patankar, J.,... Singaraja, R.R. (2018). Therapeutic modulation of the bile acid pool by cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice. The FASEB Journal, 32(7), 3792-3802. https://doi.org/10.1096/fj.201701084RR

MLA:

Chevre, Raphael, et al. "Therapeutic modulation of the bile acid pool by cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice." The FASEB Journal 32.7 (2018): 3792-3802.

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