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SIRT6 deacetylase transcriptionally regulates glucose metabolism in heart
Author(s) -
Khan Danish,
Sarikhani Mohsen,
Dasgupta Subhajit,
Maniyadath Babukrishna,
Pandit Anwit S.,
Mishra Sneha,
Ahamed Faiz,
Dubey Abhinav,
Fathma Nowrin,
Atreya Hanudatta S.,
KolthurSeetharam Ullas,
Sundaresan Nagalingam R.
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26434
Subject(s) - sirt6 , foxo1 , sirtuin , pdk4 , nad+ kinase , biology , histone deacetylase , transcription factor , hdac1 , microbiology and biotechnology , metabolism , endocrinology , biochemistry , histone , enzyme , pyruvate dehydrogenase complex , gene
Sirtuins are a family of enzymes, which govern a number of cellular processes essential for maintaining physiological balance. SIRT6, a nuclear sirtuin, is implicated in the development of metabolic disorders. The role of SIRT6 in regulation of cardiac metabolism is unexplored. Although glucose is not the primary energy source of heart, defects in glucose oxidation have been linked to heart failure. SIRT6 +/− mice hearts exhibit increased inhibitory phosphorylation of PDH subunit E1α. SIRT6 deficiency enhances FoxO1 nuclear localization that results in increased expression of PDK4. We show that SIRT6 transcriptionally regulates the expression of PDK4 by binding to its promoter. SIRT6 +/− hearts show accumulation of lactate, indicating compromised mitochondrial oxidation. SIRT6 deficiency results in decreased oxygen consumption rate and concomitantly lesser ATP production. Mechanistically, SIRT6 deficiency leads to increased FoxO1‐mediated transcription of PDK4. Our findings establish a novel link between SIRT6 and cardiac metabolism, suggesting a protective role of SIRT6 in maintaining cardiac homeostasis.