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

Mon, 2016-01-25 10:34 -- voskuhlt
TitleA Diet-Sensitive BAF60a-Mediated Pathway Links Hepatic Bile Acid Metabolism to Cholesterol Absorption and Atherosclerosis.
Publication TypeJournal Article
Year of Publication2015
AuthorsMeng Z-X, Wang L, Chang L, Sun J, Bao J, Li Y, Y Chen E, Lin JD
JournalCell Rep
Volume13
Issue8
Pagination1658-69
Date Published2015 Nov 24
ISSN2211-1247
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.

DOI10.1016/j.celrep.2015.10.033
Alternate JournalCell Rep
PubMed ID26586440
PubMed Central IDPMC4662911
Grant ListR01 DK077086 / DK / NIDDK NIH HHS / United States
R01 DK095151 / DK / NIDDK NIH HHS / United States
R01 HL068878 / HL / NHLBI NIH HHS / United States
R01 HL105114 / HL / NHLBI NIH HHS / United States
R01 HL122664 / HL / NHLBI NIH HHS / United States