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

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 non-diabetic subjects with varying levels of BMI.Methods: Human ASCs were isolated from paired SAT and VAT biopsies obtained from 83 of non-diabetic subjects and 92 obese individuals.Results: Visceral but not subcutaneous ASCs from obese subjects showed an intrinsic increase in both adipogenesis and lipid accumulation when compared to 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 non-obese 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:These observations indicate that reduced SIRT1 and SIRT2 expression in visceral ASCs may promote visceral adipose tissue expansion in human obesity by enhancing the differentiation capacity of these adipocyte precursors.

Gegen Qinlian Decoction Coordinately Regulates PPARγ and PPARα to Improve Glucose and Lipid Homeostasis in Diabetic Rats and Insulin Resistance 3T3-L1 Adipocytes

“…Activated PPARa increased Lpl expression to decompose TG into fatty acids, and elevated Cpt-1a, Mcad, Lcad, and Acox1 expression to accelerate fatty acid oxidation. The mRNA expression of SIRT1 was decreased in WAT of diabetic SD rats and IR-3T3-L1 adipocytes, it is consistent that reduced expression of SIRT1 in human obesity may foster visceral adipose tissue expansion (Perrini et al, 2020). GQD also increased the expression of histone deacetylase SIRT1, which may inhibit adipocyte differentiation including PPARg adipogenesis activity and initiate a broad program of mitochondrial gene expression and thermogenesis (Tang, 2016).…”

Tuning Adipogenic Differentiation in ADSCs by Metformin and Vitamin D: Involvement of miRNAs

“…We then evaluated the effect of metformin and vitamin D in the modulation of epigenetic genes, HDAC1 and Sirtuins. Other authors previously described that reduced HDAC1, SIRT1, and SIRT2 expression promotes adipogenesis and accumulation of visceral fat in human obesity [ 46 , 47 ]. Here, we show that ADSC exposure to metformin and vitamin D increases the expression of all the above-mentioned epigenetic modulators ( Figure 3 ), suggesting their involvement in blocking adipogenic differentiation.…”

The role of SIRT2 in cancer: A novel therapeutic target

“…Some others found by snRNA-seq SIRT2 expression level is extremely high in some specific groups of cells in the cancer tissues with SIRT2-low expression level in general. 17 Studies have found that SIRT2 is highly expressed in renal cancer cells, and patients with higher levels of SIRT2 have a worse prognosis than patients with lower levels of SIRT2 expression. SIRT2 can promote tumor cells to form clumps, so tumor cells are more resistant to fluorescenceinduced apoptosis, and after kidney transplantation, patients with high levels of SIRT2 expression are less likely to have tumor recurrence than those with SIRT2 expression Patient is taller.…”