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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 PPARγ2K382Q (a mimic of acetylated K) accumulated much less fat than adipocytes expressing wild-type PPARγ2 or PPARγ2K382R (a mimic of nonacetylated K). Global gene expression analysis of adipocytes expressing PPARγ2K382Q 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 PPARγ2K382Q was reduced compared with that of PPARγ2K382R .

Conclusion

Our findings indicate that SIRT7-dependent PPARγ2 deacetylation at K382 controls lipogenesis in adipocytes."xsd:string
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http://purl.uniprot.org/citations/33955199http://purl.uniprot.org/core/author"Yoshizawa T."xsd:string
http://purl.uniprot.org/citations/33955199http://purl.uniprot.org/core/author"Yamagata K."xsd:string
http://purl.uniprot.org/citations/33955199http://purl.uniprot.org/core/author"Tsuyama T."xsd:string
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http://purl.uniprot.org/citations/33955199http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33955199http://purl.uniprot.org/core/name"J Diabetes Investig"xsd:string
http://purl.uniprot.org/citations/33955199http://purl.uniprot.org/core/pages"1765-1774"xsd:string
http://purl.uniprot.org/citations/33955199http://purl.uniprot.org/core/title"SIRT7 regulates lipogenesis in adipocytes through deacetylation of PPARgamma2."xsd:string
http://purl.uniprot.org/citations/33955199http://purl.uniprot.org/core/volume"12"xsd:string
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