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Adipocyte and Cell Biology

Reduced SIRT1 and SIRT2 expression promotes adipogenesis of human visceral adipose stem cells and associates with accumulation of visceral fat in human obesity

International Journal of Obesity volume 44, pages 307–319 (2020)Cite this article

Subjects

Abstract

Background/Objectives

The histone deacetylases SIRT1 and SIRT2 have been shown to be involved in the differentiation of rodent adipocyte precursors. In light of the differences in gene expression and metabolic function of visceral (V) and subcutaneous (S) adipose tissue (AT) and their resident cells, the aim of this study was to investigate the role of SIRT1 and SIRT2 in the differentiation of adipose stem cells (ASCs) isolated from SAT and VAT biopsies of nondiabetic obese and nonobese individuals.

Methods

Human ASCs were isolated from paired SAT and VAT biopsies obtained from 83 nonobese and 92 obese subjects and were differentiated in vitro. Adipogenesis was evaluated by analyzing the lipid deposition using an image processing software, and gene expression by RT-qPCR. SIRT1 and SIRT2 protein expression was modified by using recombinant adenoviral vectors.

Results

Visceral but not subcutaneous ASCs from obese subjects showed an intrinsic increase in both adipogenesis and lipid accumulation when compared with ASCs from nonobese subjects, and this was associated with reduced SIRT1 and SIRT2 mRNA and protein levels. Moreover, adipose tissue mRNA levels of SIRT1 and SIRT2 showed an inverse correlation with BMI in the visceral but not subcutaneous depot. Overexpression of SIRT1 or SIRT2 in visceral ASCs from obese subjects resulted in inhibition of adipocyte differentiation, whereas knockdown of SIRT1 or SIRT2 in visceral ASCs from nonobese subjects enhanced this process. Changes in SIRT1 or SIRT2 expression and adipocyte differentiation were paralleled by corresponding changes in PPARG, CEBPA, and other genes marking terminal adipocyte differentiation.

Conclusions

SIRT1 and SIRT2 modulate the differentiation of human ASC. Reduced expression of SIRT1 and SIRT2 may enhance the differentiation capacity of visceral ASC in human obesity, fostering visceral adipose tissue expansion.

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Data availability

The authors declare that all data supporting the findings of this study are available within the article and its supplementary information files.

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Acknowledgements

The authors are grateful to all volunteers who participated to the study.

Funding

This work was supported by Ministero dell’Università e della Ricerca, Italy, and Progetti di Rilevante Interesse Nazionale and “con il contributo della Fondazione Cassa di Risparmio di Puglia.”

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Author notes

  1. These authors contributed equally: Sebastio Perrini, Stefania Porro

Authors and Affiliations

  1. Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy

    Sebastio Perrini, Stefania Porro, Pasquale Nigro, Angelo Cignarelli, Cristina Caccioppoli, Valentina Annamaria Genchi, Annalisa Natalicchio, Luigi Laviola & Francesco Giorgino

  2. General Surgery and Liver Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy

    Gennaro Martines, Michele De Fazio & Palma Capuano

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Contributions

SP and SPo were responsible for recruiting and characterization of subjects, designed experiments, analyzed data, and wrote the paper. PN, AC, CC, and VAG performed experiments and analyzed data; GM, MDF, and PC performed the adipose tissue biopsies; AN and LL analyzed data and discussed the manuscript. FG was responsible for recruiting and characterization of subjects, designed experiments, analyzed data, and wrote the paper. All authors discussed the results and implications and commented on the manuscript at all stages. FG is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Francesco Giorgino.

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Perrini, S., Porro, S., Nigro, P. et al. Reduced SIRT1 and SIRT2 expression promotes adipogenesis of human visceral adipose stem cells and associates with accumulation of visceral fat in human obesity. Int J Obes 44, 307–319 (2020). https://doi.org/10.1038/s41366-019-0436-7

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