Mouse SIRT3 attenuates hypertrophy-related lipid accumulation in the heart through the deacetylation of LCAD.
Cardiac hypertrophy is an adaptive response to pressure, volume stress, and loss of contractile mass from prior infarction. Metabolic changes in cardiac hypertrophy include suppression of fatty acid oxidation and enhancement of glucose utilization, which could result in lipid accumulation in the heart. SIRT3, a mitochondrial NAD+-dependent deacetylase, has been demonstrated to play a crucial role in controlling the acetylation status of many enzymes participating in energy metabolism. However, the role of SIRT3 in the pathogenesis of hypertrophy-related lipid accumulation remains unclear. In this study, hypertrophy-related lipid accumulation was investigated using a mouse cardiac hypertrophy model induced by transverse aortic constriction (TAC). We showed that mice developed heart failure six weeks after TAC. Furthermore, abnormal lipid accumulation and decreased palmitate oxidation rates were observed in the hypertrophic hearts, and these changes were particularly significant in SIRT3-KO mice. We also demonstrated that the short form of SIRT3 was downregulated in wild-type (WT) hypertrophic hearts and that this change was accompanied by a higher acetylation level of long-chain acyl CoA dehydrogenase (LCAD), which is a key enzyme participating in fatty acid oxidation. In addition, SIRT3 may play an essential role in attenuating lipid accumulation in the heart through the deacetylation of LCAD.
Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Tongshuai
T
Chen
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Junni
J
Liu
Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Na
N
Li
Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Shujian
S
Wang
Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Hui
H
Liu
Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Jingyuan
J
Li
Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Yun
Y
Zhang
Department of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong, China.
Peili
P
Bu
D000107:Acetylation; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D015536:Down-Regulation; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism; D056566:Sirtuin 3 / Q000235:genetics / Q000502:physiology*
C525046:Sirt3 protein, mouse; D019308:Palmitic Acid; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D056566:Sirtuin 3