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- Title
Sirtuin1-Mediated Deacetylation of Hypothalamic TTF-1 Contributes to the Energy Deficiency Response.
- Authors
Kang, Dasol; Yang, Hye Rim; Kim, Dong Hee; Kim, Kwang Kon; Jeong, Bora; Park, Byong Seo; Park, Jeong Woo; Kim, Jae Geun; Lee, Byung Ju
- Abstract
TTF-1 stimulates appetite by regulating the expression of agouti-related peptide (AgRP) and proopiomelanocortin (POMC) genes in the hypothalamus of starving animals. However, the mechanism underlying TTF-1's response to decreased energy levels remains elusive. Here, we provide evidence that the NAD+-dependent deacetylase, sirtuin1 (Sirt1), activates TTF-1 in response to energy deficiency. Energy deficiency leads to a twofold increase in the expression of both Sirt1 and TTF-1, leading to the deacetylation of TTF-1 through the interaction between the two proteins. The activation of Sirt1, induced by energy deficiency or resveratrol treatment, leads to a significant increase in the deacetylation of TTF-1 and promotes its nuclear translocation. Conversely, the inhibition of Sirt1 prevents these Sirt1 effects. Notably, a point mutation in a lysine residue of TTF-1 significantly disrupts its deacetylation and thus nearly completely hinders its ability to regulate AgRP and POMC gene expression. These findings highlight the importance of energy-deficiency-induced deacetylation of TTF-1 in the control of AgRP and POMC gene expression.
- Subjects
DEACETYLATION; GENE expression; PEPTIDES; SIRTUINS; PROOPIOMELANOCORTIN
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 15, p12530
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms241512530