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肥胖中国个体皮下脂肪细胞中米色脂肪生成潜能降低。

Reduced Beige Adipogenic Potential in Subcutaneous Adipocytes Derived from Obese Chinese Individuals.

作者信息

Li Han, Shen Lin, Zhang Lei, Yan Bing, Sun Tao, Guo Feng, Yin Xiao

机构信息

Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, People's Republic of China.

Shandong First Medical University, Taian, Shandong 271000, People's Republic of China.

出版信息

Diabetes Metab Syndr Obes. 2020 Jul 17;13:2551-2562. doi: 10.2147/DMSO.S248112. eCollection 2020.

Abstract

PURPOSE

Thermogenesis function has made brown/beige adipocyte an attractive target for obesity. Human brown adipose tissue activity is impaired in obesity in vivo. The present study aims to compare the differences in beige adipocyte differentiation potential of subcutaneous adipose tissue derived from normal weight and obese Chinese individuals in vitro.

METHODS

Adipose-derived stem cells (ADSCs) isolated from subcutaneous fat tissues of normal weight (NW) and obese (OB) groups were induced to differentiate into mature adipocyte with white adipocyte (WA)- and beige adipocyte (BA)-induction treatment. The expression of beige adipocyte marker protein UCP-1 and specific thermogenic genes was detected in differentiated adipocytes via Western blot and rt PCR, and the adipocyte mitochondrial function and lipolysis ability were also measured by oxygen consumption rate (OCR) and glycerol release rate, respectively.

RESULTS

Either with WA-induction or BA-induction, the expression of UCP-1 and beige adipocyte-specific thermogenic genes in differentiated adipocytes was higher in the NW compared to the OB group, followed by higher OCR and lipolysis ability in NW group than OB group. With BA-induction, expression of UCP-1 and thermogenic genes increased significantly, followed by the increasement in adipocytes OCR and lipolysis rate in NW group compared with WA-induction treatment, but no significant difference was observed in OB group.

CONCLUSION

Compromised beige adipocyte differentiation plasticity was found in subcutaneous white adipose tissue derived from obese Chinese individuals, which may be due part to the downregulation of β3-adrenergic receptor expression in adipocytes. Discovery of therapeutic agents to active brown adipose tissue through specific pathways could provide a promising approach for treating obesity in the future.

摘要

目的

产热功能使棕色/米色脂肪细胞成为治疗肥胖症的一个有吸引力的靶点。在体内肥胖状态下,人类棕色脂肪组织的活性会受损。本研究旨在比较体外培养的正常体重和肥胖中国个体皮下脂肪组织中米色脂肪细胞分化潜能的差异。

方法

从正常体重(NW)组和肥胖(OB)组的皮下脂肪组织中分离出脂肪来源干细胞(ADSCs),通过白色脂肪细胞(WA)诱导和米色脂肪细胞(BA)诱导处理,将其诱导分化为成熟脂肪细胞。通过蛋白质免疫印迹法(Western blot)和逆转录聚合酶链反应(rt PCR)检测分化脂肪细胞中米色脂肪细胞标志物蛋白解偶联蛋白1(UCP-1)和特定产热基因的表达,同时分别通过耗氧率(OCR)和甘油释放率测定脂肪细胞的线粒体功能和脂肪分解能力。

结果

无论是WA诱导还是BA诱导,与OB组相比,NW组分化脂肪细胞中UCP-1和米色脂肪细胞特异性产热基因的表达更高,且NW组的OCR和脂肪分解能力也高于OB组。BA诱导后,NW组UCP-1和产热基因的表达显著增加,脂肪细胞的OCR和脂肪分解率也高于WA诱导处理,但OB组未观察到显著差异。

结论

在肥胖中国个体的皮下白色脂肪组织中发现米色脂肪细胞分化可塑性受损,这可能部分归因于脂肪细胞中β3肾上腺素能受体表达下调。通过特定途径发现激活棕色脂肪组织的治疗药物可能为未来治疗肥胖症提供一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3980/7373414/38f8d38f70a9/DMSO-13-2551-g0001.jpg

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