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SIRT7 regulates lipogenesis in adipocytes through deacetylation of PPARγ2

AIMS/INTRODUCTION: Peroxisome proliferator‐activated receptor (PPAR)‐γ2 is a transcription factor crucial for regulating adipogenesis and glucose/lipid metabolism, and synthetic PPARγ ligands, such as thiazolidinediones, are effective oral medication for type 2 diabetes. Sirtuin 7 (SIRT7), a nicotin...

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Autores principales: Akter, Fatema, Tsuyama, Tomonori, Yoshizawa, Tatsuya, Sobuz, Shihab U., Yamagata, Kazuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504911/
https://www.ncbi.nlm.nih.gov/pubmed/33955199
http://dx.doi.org/10.1111/jdi.13567
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author Akter, Fatema
Tsuyama, Tomonori
Yoshizawa, Tatsuya
Sobuz, Shihab U.
Yamagata, Kazuya
author_facet Akter, Fatema
Tsuyama, Tomonori
Yoshizawa, Tatsuya
Sobuz, Shihab U.
Yamagata, Kazuya
author_sort Akter, Fatema
collection PubMed
description AIMS/INTRODUCTION: Peroxisome proliferator‐activated receptor (PPAR)‐γ2 is a transcription factor crucial for regulating adipogenesis and glucose/lipid metabolism, and synthetic PPARγ ligands, such as thiazolidinediones, are effective oral medication for type 2 diabetes. Sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide‐dependent deacetylase, also controls metabolism. However, it is not known whether SIRT7 regulates the function of PPARγ2 by its deacetylation. MATERIALS AND METHODS: Physical interaction between SIRT7 and PPARγ2, the effect of SIRT7 on PPARγ2 acetylation, and the deacetylation residue targeted by SIRT7 were investigated. The effects of PPARγ2 K382 acetylation on lipid accumulation, gene expression in C3H10T1/2 cell‐derived adipocytes, and ligand‐dependent transactivation activity were also evaluated. RESULTS: We demonstrated that SIRT7 binds to PPARγ2 and deacetylates PPARγ2 at K382. C3H10T1/2‐derived adipocytes expressing PPARγ2(K382Q) (a mimic of acetylated K) accumulated much less fat than adipocytes expressing wild‐type PPARγ2 or PPARγ2(K382R) (a mimic of nonacetylated K). Global gene expression analysis of adipocytes expressing PPARγ2(K382Q) revealed that K382Q caused the dysregulation of a set of genes involved in lipogenesis, including Srebp1c, Acaca, Fasn, and Scd1. The rosiglitazone‐dependent transcriptional activity of PPARγ2(K382Q) was reduced compared with that of PPARγ2(K382R). CONCLUSION: Our findings indicate that SIRT7‐dependent PPARγ2 deacetylation at K382 controls lipogenesis in adipocytes.
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spelling pubmed-85049112021-10-18 SIRT7 regulates lipogenesis in adipocytes through deacetylation of PPARγ2 Akter, Fatema Tsuyama, Tomonori Yoshizawa, Tatsuya Sobuz, Shihab U. Yamagata, Kazuya J Diabetes Investig Original Articles AIMS/INTRODUCTION: Peroxisome proliferator‐activated receptor (PPAR)‐γ2 is a transcription factor crucial for regulating adipogenesis and glucose/lipid metabolism, and synthetic PPARγ ligands, such as thiazolidinediones, are effective oral medication for type 2 diabetes. Sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide‐dependent deacetylase, also controls metabolism. However, it is not known whether SIRT7 regulates the function of PPARγ2 by its deacetylation. MATERIALS AND METHODS: Physical interaction between SIRT7 and PPARγ2, the effect of SIRT7 on PPARγ2 acetylation, and the deacetylation residue targeted by SIRT7 were investigated. The effects of PPARγ2 K382 acetylation on lipid accumulation, gene expression in C3H10T1/2 cell‐derived adipocytes, and ligand‐dependent transactivation activity were also evaluated. RESULTS: We demonstrated that SIRT7 binds to PPARγ2 and deacetylates PPARγ2 at K382. C3H10T1/2‐derived adipocytes expressing PPARγ2(K382Q) (a mimic of acetylated K) accumulated much less fat than adipocytes expressing wild‐type PPARγ2 or PPARγ2(K382R) (a mimic of nonacetylated K). Global gene expression analysis of adipocytes expressing PPARγ2(K382Q) revealed that K382Q caused the dysregulation of a set of genes involved in lipogenesis, including Srebp1c, Acaca, Fasn, and Scd1. The rosiglitazone‐dependent transcriptional activity of PPARγ2(K382Q) was reduced compared with that of PPARγ2(K382R). CONCLUSION: Our findings indicate that SIRT7‐dependent PPARγ2 deacetylation at K382 controls lipogenesis in adipocytes. John Wiley and Sons Inc. 2021-05-31 2021-10 /pmc/articles/PMC8504911/ /pubmed/33955199 http://dx.doi.org/10.1111/jdi.13567 Text en © 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Akter, Fatema
Tsuyama, Tomonori
Yoshizawa, Tatsuya
Sobuz, Shihab U.
Yamagata, Kazuya
SIRT7 regulates lipogenesis in adipocytes through deacetylation of PPARγ2
title SIRT7 regulates lipogenesis in adipocytes through deacetylation of PPARγ2
title_full SIRT7 regulates lipogenesis in adipocytes through deacetylation of PPARγ2
title_fullStr SIRT7 regulates lipogenesis in adipocytes through deacetylation of PPARγ2
title_full_unstemmed SIRT7 regulates lipogenesis in adipocytes through deacetylation of PPARγ2
title_short SIRT7 regulates lipogenesis in adipocytes through deacetylation of PPARγ2
title_sort sirt7 regulates lipogenesis in adipocytes through deacetylation of pparγ2
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504911/
https://www.ncbi.nlm.nih.gov/pubmed/33955199
http://dx.doi.org/10.1111/jdi.13567
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