脂肪组织巨噬细胞衍生的外泌体 miR-29a 调节肥胖相关的胰岛素抵抗。
Adipose tissue macrophage-derived exosomal miR-29a regulates obesity-associated insulin resistance.
机构信息
Department of Endocrinology, Changsha Central Hospital, Changsha, Hunan, 410004, China.
Division of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
出版信息
Biochem Biophys Res Commun. 2019 Jul 23;515(2):352-358. doi: 10.1016/j.bbrc.2019.05.113. Epub 2019 May 29.
Obesity-associated insulin resistance is a forerunner of type 2 diabetes. Macrophages reside within adipose tissue (ATMs) have been reported to regulate insulin sensitivity through secreting miRNAs containing exosomes. Here, we show that miR-29a is increased in obese ATMs derived exosomes (ATMs-Exos) and can be transferred into adipocytes, myocytes and hepatocytes causing insulin resistance in vitro and in vivo. Administration of obese ATMs-Exos impairs insulin sensitivity of lean mice. While knockdown miR-29a level in obese ATM-Exos blunts this effect. PPAR-δ is identified to function as downstream target of miR-29a in regulating insulin resistance. PPAR-δ agonist GW501516 partially rescued the insulin resistance induced by miR-29a. Taken together, these findings suggest that ATMs derived exosomal miR-29a could regulate obesity-associated insulin resistance, which may serve as a potential therapeutic target for obesity-associated type 2 diabetes.
肥胖相关的胰岛素抵抗是 2 型糖尿病的前兆。据报道，脂肪组织（ATMs）中的巨噬细胞通过分泌含有外泌体的 miRNAs 来调节胰岛素敏感性。在这里，我们表明，肥胖 ATMs 衍生的外泌体（ATMs-Exos）中 miR-29a 的水平增加，并且可以转移到脂肪细胞、肌细胞和肝细胞中，导致体内和体外的胰岛素抵抗。给予肥胖 ATMs-Exos 会损害瘦鼠的胰岛素敏感性。而在肥胖 ATM-Exos 中敲低 miR-29a 水平则会减弱这种作用。PPAR-δ 被鉴定为 miR-29a 在调节胰岛素抵抗中的下游靶标。PPAR-δ 激动剂 GW501516 部分挽救了 miR-29a 诱导的胰岛素抵抗。总之，这些发现表明，ATMs 衍生的外泌体 miR-29a 可以调节肥胖相关的胰岛素抵抗，这可能成为肥胖相关 2 型糖尿病的潜在治疗靶点。
Zotero 插件