A Diet-Sensitive BAF60a-Mediated Pathway Links Hepatic Bile Acid Metabolism to Cholesterol Absorption and Atherosclerosis

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2015 Nov 21

PMID 26586440

Citations 21

Authors

Zhuo-Xian Meng

Lin Wang

Lin Chang

Jingxia Sun

Jiangyin Bao

Yaqiang Li

Y Eugene Chen

Jiandie D Lin

Affiliations

Soon will be listed here.

Abstract

Dietary nutrients interact with gene networks to orchestrate adaptive responses during metabolic stress. Here, we identify Baf60a as a diet-sensitive subunit of the SWI/SNF chromatin-remodeling complexes in the mouse liver that links the consumption of fat- and cholesterol-rich diet to elevated plasma cholesterol levels. Baf60a expression was elevated in the liver following feeding with a western diet. Hepatocyte-specific inactivation of Baf60a reduced bile acid production and cholesterol absorption, and attenuated diet-induced hypercholesterolemia and atherosclerosis in mice. Baf60a stimulates expression of genes involved in bile acid synthesis, modification, and transport through a CAR/Baf60a feedforward regulatory loop. Baf60a is required for the recruitment of the SWI/SNF chromatin-remodeling complexes to facilitate an activating epigenetic switch on target genes. These studies elucidate a regulatory pathway that mediates the hyperlipidemic and atherogenic effects of western diet consumption.

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