Khan, D and Ara, T and Ravi, V and Rajagopal, R and Tandon, H and Parvathy, J and Gonzalez, EA and Asirvatham-Jeyaraj, N and Krishna, S and Mishra, S and Raghu, S and Bhati, AS and Tamta, AK and Dasgupta, S and Kolthur-Seetharam, U and Etchegaray, J-P and Mostoslavsky, R and Rao, PSM and Srinivasan, N and Sundaresan, NR (2021) SIRT6 transcriptionally regulates fatty acid transport by suppressing PPARγ. In: Cell Reports, 35 (9).
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Abstract
Pathological lipid accumulation is often associated with enhanced uptake of free fatty acids via specific transporters in cardiomyocytes. Here, we identify SIRT6 as a critical transcriptional regulator of fatty acid transporters in cardiomyocytes. We find that SIRT6 deficiency enhances the expression of fatty acid transporters, leading to enhanced fatty acid uptake and lipid accumulation. Interestingly, the haploinsufficiency of SIRT6 is sufficient to induce the expression of fatty acid transporters and cause lipid accumulation in murine hearts. Mechanistically, SIRT6 depletion enhances the occupancy of the transcription factor PPARγ on the promoters of critical fatty acid transporters without modulating the acetylation of histone 3 at Lys 9 and Lys 56. Notably, the binding of SIRT6 to the DNA-binding domain of PPARγ is critical for regulating the expression of fatty acid transporters in cardiomyocytes. Our data suggest exploiting SIRT6 as a potential therapeutic target for protecting the heart from metabolic diseases. © 2021 The Authors
| Item Type: | Journal Article |
|---|---|
| Publication: | Cell Reports |
| Publisher: | Elsevier B.V. |
| Additional Information: | The copyright for this article belongs to Authors |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Microbiology & Cell Biology Division of Physical & Mathematical Sciences > Mathematics |
| Date Deposited: | 30 Aug 2021 10:28 |
| Last Modified: | 30 Aug 2021 10:28 |
| URI: | http://eprints.iisc.ac.in/id/eprint/69499 |
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