SIRT1 和 SIRT2 表达减少促进人内脏脂肪干细胞的脂肪生成，并与人类肥胖内脏脂肪的积累相关。
Reduced SIRT1 and SIRT2 expression promotes adipogenesis of human visceral adipose stem cells and associates with accumulation of visceral fat in human obesity.
机构信息
Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.
General Surgery and Liver Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy.
出版信息
Int J Obes (Lond). 2020 Feb;44(2):307-319. doi: 10.1038/s41366-019-0436-7. Epub 2019 Aug 28.
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.
背景/目的：组蛋白去乙酰化酶 SIRT1 和 SIRT2 已被证明参与了啮齿类动物脂肪细胞前体的分化。鉴于内脏（V）和皮下（S）脂肪组织（AT）及其驻留细胞的基因表达和代谢功能存在差异，本研究旨在探讨 SIRT1 和 SIRT2 在分离自非肥胖和肥胖个体的 SAT 和 VAT 活检的脂肪干细胞（ASC）分化中的作用。
方法
从 83 名非肥胖和 92 名肥胖个体的 SAT 和 VAT 活检中分离人 ASC，并在体外进行分化。通过图像处理软件分析脂质沉积来评估脂肪生成，并用 RT-qPCR 分析基因表达。使用重组腺病毒载体来修饰 SIRT1 和 SIRT2 蛋白表达。
结果
与非肥胖个体的 ASC 相比，肥胖个体的内脏 ASC 而非皮下 ASC 固有地增加了脂肪生成和脂质积累，这与 SIRT1 和 SIRT2 mRNA 和蛋白水平降低有关。此外，SIRT1 和 SIRT2 在脂肪组织中的 mRNA 水平与内脏脂肪组织中的 BMI 呈负相关，但与皮下脂肪组织无关。在肥胖个体的内脏 ASC 中过表达 SIRT1 或 SIRT2 会抑制脂肪细胞分化，而在非肥胖个体的内脏 ASC 中敲低 SIRT1 或 SIRT2 则增强了这一过程。SIRT1 或 SIRT2 表达的变化和脂肪细胞分化与标记终末脂肪细胞分化的其他基因如 PPARG、CEBPA 等的变化平行。
结论
SIRT1 和 SIRT2 调节人 ASC 的分化。SIRT1 和 SIRT2 表达的减少可能增强了人类肥胖中内脏 ASC 的分化能力，促进了内脏脂肪组织的扩张。
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