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人类皮下脂肪组织与内脏脂肪组织之间的端粒长度差异。

Telomere length differences between subcutaneous and visceral adipose tissue in humans.

作者信息

Lakowa Nicole, Trieu Nhu, Flehmig Gesine, Lohmann Tobias, Schön Michael R, Dietrich Arne, Zeplin Philip Helge, Langer Stefan, Stumvoll Michael, Blüher Matthias, Klöting Nora

机构信息

Department of Medicine, University of Leipzig, Leipzig, Germany.

Municipal Clinic Dresden-Neustadt, Dresden, Germany.

出版信息

Biochem Biophys Res Commun. 2015 Feb 13;457(3):426-32. doi: 10.1016/j.bbrc.2014.12.122. Epub 2015 Jan 13.

Abstract

Adipocyte hypertrophy and hyperplasia have been shown to be associated with shorter telomere length, which may reflect aging, altered cell proliferation and adipose tissue (AT) dysfunction. In individuals with obesity, differences in fat distribution and AT cellular composition may contribute to obesity related metabolic diseases. Here, we tested the hypotheses that telomere lengths (TL) are different between: (1) abdominal subcutaneous and omental fat depots, (2) superficial and deep abdominal subcutaneous AT (SAT), and (3) adipocytes and cells of the stromal vascular fraction (SVF). We further asked whether AT TL is related to age, anthropometric and metabolic traits. TL was analyzed by quantitative PCR in total human genomic DNA isolated from paired subcutaneous and visceral AT of 47 lean and 50 obese individuals. In subgroups, we analyzed TL in isolated small and large adipocytes and SVF cells. We find significantly shorter TL in subcutaneous compared to visceral AT (P < 0.001) which is consistent in men and subgroups of lean and obese, and individuals with or without type 2 diabetes (T2D). Shorter TL in SAT is entirely due to shorter TL in the SVF compared to visceral AT (P < 0.01). SAT TL is most strongly correlated with age (r = -0.205, P < 0.05) and independently of age with HbA1c (r = -0.5, P < 0.05). We found significant TL differences between superficial SAT of lean and obese as well as between individuals with our without T2D, but not between the two layers of SAT. Our data indicate that fat depot differences in TL mainly reflect shorter TL of SVF cells. In addition, we found an age and BMI-independent relationship between shorter TL and HbA1c suggesting that chronic hyperglycemia may impair the regenerative capacity of AT more strongly than obesity alone.

摘要

脂肪细胞肥大和增生已被证明与较短的端粒长度有关,这可能反映了衰老、细胞增殖改变和脂肪组织(AT)功能障碍。在肥胖个体中,脂肪分布和AT细胞组成的差异可能导致与肥胖相关的代谢疾病。在此,我们检验了以下假设:端粒长度(TL)在以下情况之间存在差异:(1)腹部皮下和网膜脂肪库;(2)腹部皮下AT(SAT)的浅层和深层;(3)脂肪细胞和基质血管部分(SVF)的细胞。我们还询问了AT TL是否与年龄、人体测量和代谢特征相关。通过定量PCR分析了从47名瘦人和50名肥胖个体的配对皮下和内脏AT中分离的总人类基因组DNA中的TL。在亚组中,我们分析了分离的小脂肪细胞和大脂肪细胞以及SVF细胞中的TL。我们发现,与内脏AT相比,皮下AT的TL显著更短(P < 0.001),这在男性、瘦人和肥胖亚组以及有或无2型糖尿病(T2D)的个体中都是一致的。SAT中较短的TL完全是由于与内脏AT相比,SVF中的TL更短(P < 0.01)。SAT TL与年龄的相关性最强(r = -0.205,P < 0.05),并且独立于年龄与糖化血红蛋白(HbA1c)相关(r = -0.5,P < 0.05)。我们发现瘦人和肥胖者的浅层SAT之间以及有或无T2D的个体之间TL存在显著差异,但SAT的两层之间没有差异。我们的数据表明,TL的脂肪库差异主要反映了SVF细胞的TL更短。此外,我们发现较短的TL与HbA1c之间存在独立于年龄和BMI的关系,这表明慢性高血糖可能比单独肥胖更强烈地损害AT的再生能力。

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