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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Meng ZX,Wang L,Chang L,Sun J,Bao J,Li Y,Chen YE,Lin JDdoi
10.1016/j.celrep.2015.10.033subject
Has Abstractpub_date
2015-11-24 00:00:00pages
1658-69issue
8issn
2211-1247pii
S2211-1247(15)01203-6journal_volume
13pub_type
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