The pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function

• Published in: Cell death & disease Vol. 10; no. 2; p. 66
• Main Authors: Zhang, Yuqing, Zhou, Feiye, Bai, Mengyao, Liu, Yun, Zhang, Linlin, Zhu, Qin, Bi, Yufang, Ning, Guang, Zhou, Libin, Wang, Xiao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.01.2019; Springer Nature B.V
• Subjects: 13/106; 631/337/458/1275; 64/60; 692/163/2743/137/773; 82/58; 96/1; 96/44; Acetylation; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Energy metabolism; Enzyme Stability; Enzymes; Fasting; Fatty acids; Fatty Acids - metabolism; Glucose; Glucose - metabolism; HEK293 Cells; Humans; Immunology; Insulin; Insulin secretion; Insulin Secretion - physiology; Insulin-Secreting Cells - physiology; Life Sciences; Male; Metabolic pathways; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; Mitochondrial Trifunctional Protein, alpha Subunit - metabolism; Oxidation; Oxidation-Reduction; Palmitic acid; Protein turnover; Proteins; Rats; Rats, Sprague-Dawley; Secretion; Sirtuin 3 - genetics; Sirtuin 3 - metabolism; Sirtuins - metabolism; Transfection
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1349-z

Protein acetylation has a crucial role in energy metabolism. Here we performed the first large-scale profiling of acetylome in rat islets, showing that almost all enzymes in core metabolic pathways related to insulin secretion were acetylated. Label-free quantitative acetylome of islets in response to high glucose revealed hyperacetylation of enzymes involved in fatty acid β-oxidation (FAO), including trifunctional enzyme subunit alpha (ECHA). Acetylation decreased the protein stability of ECHA and its ability to promote FAO. The overexpression of SIRT3, a major mitochondrial deacetylase, prevented the degradation of ECHA via decreasing its acetylation level in β-cells. SIRT3 expression was upregulated in rat islets upon exposure to low glucose or fasting. SIRT3 overexpression in islets markedly decreased palmitate-potentiated insulin secretion, whereas islets from SIRT3 knockout mice secreted more insulin, with an opposite action on FAO. ECHA overexpression partially reversed SIRT3 deficiency-elicited insulin hypersecretion. Our study highlights the potential role of protein acetylation in insulin secretion.