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Journal article
Impact of a High-fat Diet on Tissue Acyl-CoA and Histone Acetylation LevelsThis work was supported by American Diabetes Association Grant 7-12-JF-59, NCI, National Institutes of Health Grant R01CA174761, by a Pancreatic Cancer Action Network-American Association for Cancer Research Career Development Award (to K. E. W.), by the Abramson Cancer Center Basic Science Center for Excellence in Cancer Metabolism (to K. E. W. and I. A. B.), by National Institutes of Health Grants R21HD087866 and K22ES2
The Journal of biological chemistry, Vol.292(8), pp.3312-3322
24 Feb 2017
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood but could alter gene expression and influence metabolic health. ATP citrate-lyase produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types. Consumption of a high-fat diet (HFD) results in suppression of ATP citrate-lyase levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown. Here we examined the effects of HFD on levels of acyl-CoAs and histone acetylation in mouse white adipose tissue (WAT), liver, and pancreas. We report that mice consuming a HFD have reduced levels of acetyl-CoA and/or acetyl-CoA:CoA ratio in these tissues. In WAT and the pancreas, HFD also impacted the levels of histone acetylation; in particular, histone H3 lysine 23 acetylation was lower in HFD-fed mice. Genetic deletion of Acly in cultured adipocytes also suppressed acetyl-CoA and histone acetylation levels. In the liver, no significant effects on histone acetylation were observed with a HFD despite lower acetyl-CoA levels. Intriguingly, acetylation of several histone lysines correlated with the acetyl-CoA: (iso)butyryl-CoA ratio in liver. Butyryl-CoA and isobutyryl-CoA interacted with the acetyltransferase P300/CBP-associated factor (PCAF) in liver lysates and inhibited its activity in vitro. This study thus provides evidence that diet can impact tissue acyl-CoA and histone acetylation levels and that acetyl-CoA abundance correlates with acetylation of specific histone lysines in WAT but not in the liver.
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Details
- Title
- Impact of a High-fat Diet on Tissue Acyl-CoA and Histone Acetylation LevelsThis work was supported by American Diabetes Association Grant 7-12-JF-59, NCI, National Institutes of Health Grant R01CA174761, by a Pancreatic Cancer Action Network-American Association for Cancer Research Career Development Award (to K. E. W.), by the Abramson Cancer Center Basic Science Center for Excellence in Cancer Metabolism (to K. E. W. and I. A. B.), by National Institutes of Health Grants R21HD087866 and K22ES2
- Creators
- Alessandro Carrer - Cancer Research InstituteJoshua L.D. Parris - Cancer Research InstituteSophie Trefely - Drexel UniversityRyan A. Henry - Fox Chase Cancer CenterDavid C. Montgomery - National Cancer InstituteAnnMarie Torres - Cancer Research InstituteJohn M. Viola - Cancer Research InstituteYin-Ming Kuo - Fox Chase Cancer CenterIan A. Blair - Translational TherapeuticsJordan L. Meier - National Cancer InstituteAndrew J. Andrews - Fox Chase Cancer CenterNathaniel W. Snyder - Drexel UniversityKathryn E. Wellen - Cancer Research Institute
- Publication Details
- The Journal of biological chemistry, Vol.292(8), pp.3312-3322
- Publisher
- Elsevier
- Grant note
- 7-12-JF-59 / American Diabetes Association R01CA174761 / NCI, National Institutes of Health R21HD087866 and K22ES26235 / National Institutes of Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Identifiers
- 991019168087904721
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- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology