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

• Published in: International Journal of Obesity Vol. 44; no. 2; pp. 307 - 319
• Main Authors: Perrini, Sebastio, Porro, Stefania, Nigro, Pasquale, Cignarelli, Angelo, Caccioppoli, Cristina, Genchi, Valentina Annamaria, Martines, Gennaro, De Fazio, Michele, Capuano, Palma, Natalicchio, Annalisa, Laviola, Luigi, Giorgino, Francesco
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2020; Nature Publishing Group
• Subjects: 13; 13/100; 13/106; 13/95; 14; 38; 38/44; 38/77; 38/90; 42; 45; 45/29; 631/208/135; 631/80/458; Accumulation; Adipocytes; Adipocytes - metabolism; Adipogenesis; Adipogenesis - physiology; Adipose tissue; Adipose tissues; Adult; Biopsy; Cell differentiation; Cells, Cultured; Computer programs; Differentiation; Epidemiology; Expression vectors; Female; Gene expression; Gene Knockdown Techniques; Genes; Health Promotion and Disease Prevention; Histones; Humans; Image processing; Internal Medicine; Intra-Abdominal Fat - cytology; Intra-Abdominal Fat - metabolism; Lipids; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Obesity; Obesity - metabolism; Peroxisome proliferator-activated receptors; Proteins; Public Health; RNA; SIRT1 protein; Sirtuin 1 - analysis; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Sirtuin 2 - analysis; Sirtuin 2 - genetics; Sirtuin 2 - metabolism; Stem cell transplantation; Stem cells; Stem Cells - metabolism; Type 2 diabetes
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-019-0436-7

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.