Department of Gastroenterology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Endocr J. 2023 Jun 28;70(6):581-589. doi: 10.1507/endocrj.EJ22-0288. Epub 2023 Apr 5.
Adipocyte apoptosis is a key initial event that contributes to macrophage infiltration into adipose tissue (AT) and thus triggers AT inflammation in obesity. MicroRNA-27a (miR-27a) was shown to mediate the pathological processes of many metabolic disorders; however, whether miR-27a is involved in adipocyte apoptosis of obese AT remains unknown. The present study aimed to investigate the alteration of miR-27a in obese individuals and its antiapoptotic function in adipocytes. In vivo, serum samples and omental adipose tissue from humans as well as epididymal fat pads from mice were collected to detect miR-27a expression. In vitro, 3T3-L1 preadipocytes and mature adipocytes were treated with TNF-α to induce apoptosis and transfected with a mimic for overexpressing miR-27a-3p. The results showed that miR-27a was markedly decreased in the serum and AT of obese human patients and in the AT of high-fat diet-fed mice. Regression analyses revealed that the serum level of miR-27a was correlated with metabolic parameters in human obesity. Notably, TNF-α induced cell apoptosis in both preadipocytes and mature adipocytes, as evidenced by the upregulation of cleaved caspase 3 and cleaved caspase 8 and the ratio of Bax to Bcl-2, while these effects were partly diminished by miR-27a overexpression. In addition, TUNEL and Hoechst 33258 staining verified that miR-27a overexpression markedly inhibited the apoptosis of adipocytes under TNF-α stimulation. Thus, miR-27a was downregulated in the AT of obese subjects with proapoptotic status, and overexpression of miR-27a exerted an antiapoptotic effect on preadipocytes, providing a novel potential target for preventing AT dysfunction.
脂肪细胞凋亡是导致巨噬细胞浸润脂肪组织（AT）并触发肥胖 AT 炎症的关键初始事件。microRNA-27a（miR-27a）被证明介导许多代谢紊乱的病理过程；然而，miR-27a 是否参与肥胖 AT 中的脂肪细胞凋亡尚不清楚。本研究旨在研究肥胖个体中 miR-27a 的变化及其在脂肪细胞中的抗凋亡功能。在体内，收集人类血清样本和网膜脂肪组织以及小鼠附睾脂肪垫，以检测 miR-27a 的表达。在体外，用 TNF-α处理 3T3-L1 前脂肪细胞和成熟脂肪细胞，以诱导细胞凋亡，并转染 miR-27a-3p 的模拟物以过表达 miR-27a。结果表明，肥胖患者的血清和 AT 以及高脂肪饮食喂养的小鼠的 AT 中 miR-27a 明显降低。回归分析显示，血清 miR-27a 水平与人类肥胖的代谢参数相关。值得注意的是，TNF-α诱导前脂肪细胞和成熟脂肪细胞凋亡，证据是 cleaved caspase 3 和 cleaved caspase 8 的上调以及 Bax 与 Bcl-2 的比值，而这些效应部分被 miR-27a 过表达减弱。此外，TUNEL 和 Hoechst 33258 染色证实，miR-27a 过表达显著抑制 TNF-α刺激下脂肪细胞的凋亡。因此，肥胖患者的 AT 中 miR-27a 呈下调状态，miR-27a 过表达对前脂肪细胞具有抗凋亡作用，为预防 AT 功能障碍提供了新的潜在靶点。
