Department of Endocrinology and Metabolism, Jinan Central Hospital, Jinan, China,
Cheeloo College of Medicine, Shandong University, Jinan, China,
Obes Facts. 2022;15(3):442-450. doi: 10.1159/000523871. Epub 2022 Mar 23.
Introdution and Aims: The myokine irisin is critical to modulating adipocytes thermogenesis and influence whole-body metabolism. However, whether there is difference in the effects of irisin on adipocytes derived from different depots remains unknown, and the receptor of irisin on adipocytes is still unclear. In this study, we determine the browning effect of irisin on adipocytes of subcutaneous and visceral human adipose tissue and explore the possibility that integrin αV was the receptor of irisin on human adipocytes.
Human adipose-derived stem cells were isolated from human subcutaneous and visceral white adipose tissues and induced to differentiate into mature adipocytes, and the expression of UCP1 and thermogenic genes in mature adipocytes were examined with or without irisin treatment and compared between groups of different adiposity and different spots. Immunoprecipitation analysis was used to detect the interaction between irisin and integrin αV on adipocytes, and the protein expression of integrin αV in adipocytes was also compared between groups of different adiposity and anatomic position.
Irisin treatment could increase the expression level of beige adipocyte marker protein UCP1 and specific thermogenic genes in mature adipocytes derived from subcutaneous white adipose tissue but not in visceral adipose tissue. The results of immunoprecipitation showed that irisin could be attached to integrin αV on mature adipocytes, and there was no significant difference in the gene and protein expression of integrin αV in adipocytes, either derived from subcutaneous and visceral adipose tissue, or derived from obese and normal-weight individuals.
The results of the present study indicated that irisin contributed to the transformation of mature white adipocytes to beige adipocytes in human subcutaneous adipose tissue but not in visceral adipose tissue. Integrin αV may mediate the browning effects of irisin on human mature adipocytes, which could provide the potential therapeutic targets for obesity and metabolic syndrome by promoting human brown adipose tissue activity.
鸢尾素是调节脂肪细胞产热和影响全身代谢的关键因子。然而,鸢尾素对不同部位来源的脂肪细胞的作用是否存在差异尚不清楚,鸢尾素在脂肪细胞上的受体也尚不清楚。本研究旨在确定鸢尾素对人体皮下和内脏白色脂肪组织来源的脂肪细胞的棕色化作用,并探讨整合素 αV 可能是鸢尾素在人脂肪细胞上的受体。
从人体皮下和内脏白色脂肪组织中分离出脂肪源性干细胞,并诱导其分化为成熟脂肪细胞,用或不用鸢尾素处理后,检测成熟脂肪细胞中 UCP1 和产热基因的表达,并比较不同体脂和不同部位的组间差异。免疫沉淀分析用于检测鸢尾素与脂肪细胞上整合素 αV 的相互作用,比较不同体脂和不同部位的组间脂肪细胞中整合素 αV 的蛋白表达。
鸢尾素处理可增加来源于皮下白色脂肪组织的成熟脂肪细胞中 beige 脂肪细胞标志物蛋白 UCP1 和特定产热基因的表达水平,但对来源于内脏脂肪组织的成熟脂肪细胞无此作用。免疫沉淀结果表明,鸢尾素可与成熟脂肪细胞上的整合素 αV 结合,来源于皮下和内脏脂肪组织的脂肪细胞,以及来源于肥胖和正常体重个体的脂肪细胞中,整合素 αV 的基因和蛋白表达均无显著差异。
本研究结果表明,鸢尾素有助于人体皮下白色脂肪组织中成熟白色脂肪细胞向 beige 脂肪细胞的转化,但对内脏白色脂肪组织无此作用。整合素 αV 可能介导鸢尾素对人成熟脂肪细胞的棕色化作用,通过促进人体棕色脂肪组织活性,为肥胖和代谢综合征提供潜在的治疗靶点。