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Role of acetyl‐CoA metabolizing enzyme ACSS2 and dietary acetyl‐CoA precursors in transcription and lipid disorder
Author(s) -
Moreau Regis,
Erickson Anjeza,
Bruner Noel,
Xia Mengna,
He Bo
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.691.20
Subject(s) - acetylation , histone , lipogenesis , biochemistry , lipid metabolism , gene expression , biology , chemistry , gene
Dyslipidemia and fatty liver that occur secondarily to obesity result from extensive gene expression changes in tissues throughout the body. By converting acetate into acetyl‐CoA, acetyl‐CoA synthetase 2 (ACSS2, cytoplasmic) raises the levels of acetyl‐CoA with an expected impact on histone acetylation and lipid production. We created two stable AML12 liver cell lines that exhibit normal or high (mRNA, +1300%; protein, +1600%) levels of ACSS2 and in this model asked how dietary precursors of acetyl‐CoA modulate histone acetylation and lipid metabolism. ACSS2 raised global histone H3 acetylation (+53%), increased fatty acid synthase abundance (+67%), and induced albumin expression (cellular, +643%; secreted, +284%). Acetate further stimulated histone H3 acetylation (+96%) and albumin expression (+473%). In the present study, we further investigate the regulation of these genes by ACSS2 in the presence of acetate and ethanol. Our results provide new insights into how precursors of acetyl‐CoA found in our diet regulate transcription in an ACSS2 dependent manner. The long‐term goal of this study is to identify diet‐dependent epigenetic mechanisms that modulate lipid risk factors for cardiovascular diseases and hepatosteatosis. Support or Funding Information Supported by UNL Hatch Act, Tobacco Settlement Funds, UNL UCARE Program, and Allen Foundation.