Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia

• DOI: 10.1038/ncomms11960
• Publication Date: 2016-06-30T09:04:48Z
• Authors: Xue Gao; Shu-Hai Lin; Feng Ren; Jin-Tao Li; Jia-Jia Chen; Chuan-Bo Yao; Hong-Bin Yang; Shu-Xia Jiang; Guo-Quan Yan; Di Wang; Yi Wang; Ying Liu; Zongwei Cai; Ying-Ying Xu; Jing Chen; Wenqiang Yu; Peng-Yuan Yang; Qun-Ying Lei
• Keywords: Fatty acid synthesis

Abstract Besides the conventional carbon sources, acetyl-CoA has recently been shown to be generated from acetate in various types of cancers, where it promotes lipid synthesis and tumour growth. The underlying mechanism, however, remains largely unknown. We find that induces a hyperacetylated state histone H3 hypoxic cells. Acetate predominately activates lipogenic genes ACACA FASN expression by increasing H3K9, H3K27 H3K56 acetylation levels at their promoter regions, thus enhancing de novo synthesis, which combines with its function as metabolic precursor for fatty acid synthesis. Acetyl-CoA synthetases (ACSS1, ACSS2) are involved this acetate-mediated epigenetic regulation. More importantly, human hepatocellular carcinoma high ACSS1/2 exhibit increased expression. Taken together, study demonstrates acetate, addition ability induce an immediate precursor, also functions metabolite promote cancer cell survival under stress.