Hepatic conversion of acetyl-CoA to acetate plays crucial roles in energy stress

作者：Jinyang Wang, Yaxin Wen, Wentao Zhao, Yan Zhang, Furong Lin, Cong Ouyang, Huihui Wang, Lizheng Yao, Huanhuan Ma, Zhuo Yue, Huiying Huang, Xiulin Shi, Liubin Feng, Donghai Lin, Bin Jiang, Qinxi Li · 发表于：eLife · 年份：2023 · DOI：10.7554/elife.87419.3 · 被引用次数：14 · 研究领域：Diet and metabolism studies、Diet, Metabolism, and Disease、Adipose Tissue and Metabolism

Accumulating evidence indicates that acetate is increased under energy stress conditions such as those that occur in diabetes mellitus and prolonged starvation. However, how and where acetate is produced and the nature of its biological significance are largely unknown. We observed overproduction of acetate to concentrations comparable to those of ketone bodies in patients and mice with diabetes or starvation. Mechanistically, ACOT12 and ACOT8 are dramatically upregulated in the liver to convert free fatty acid-derived acetyl-CoA to acetate and CoA. This conversion not only provides a large amount of acetate, which preferentially fuels the brain rather than muscle, but also recycles CoA, which is required for sustained fatty acid oxidation and ketogenesis. We suggest that acetate is an emerging novel ‘ketone body’ that may be used as a parameter to evaluate the progression of energy stress.