PDF(Pubmed)
Abstract：
Adipose tissue macrophages (ATMs) influence obesity-associated metabolic dysfunction, but the mechanisms by which they do so are not well understood. We show that miR-6236 is a bona fide miRNA that is secreted by ATMs during obesity. Global or myeloid cell-specific deletion of miR-6236 aggravates obesity-associated adipose tissue insulin resistance, hyperglycemia, hyperinsulinemia, and hyperlipidemia. miR-6236 augments adipocyte insulin sensitivity by inhibiting translation of negative regulators of insulin signaling, including PTEN. The human genome harbors a miR-6236 homolog that is highly expressed in the serum and adipose tissue of obese people. hsa-MIR-6236 expression negatively correlates with hyperglycemia and glucose intolerance, and positively correlates with insulin sensitivity. Together, our findings establish miR-6236 as an ATM-secreted miRNA that potentiates adipocyte insulin signaling and protects against metabolic dysfunction during obesity.
摘要：
脂肪组织巨噬细胞（ATM）影响肥胖相关的代谢功能障碍，但是他们这样做的机制还没有得到很好的理解。我们发现miR-6236是肥胖期间ATM分泌的真正miRNA。miR-6236的全局或髓样细胞特异性缺失加重肥胖相关脂肪组织胰岛素抵抗,高血糖症,高胰岛素血症,和高脂血症。miR-6236通过抑制胰岛素信号的负调节因子的翻译来增强脂肪细胞的胰岛素敏感性，包括PTEN。人类基因组包含miR-6236同源物，该同源物在肥胖者的血清和脂肪组织中高度表达。hsa-MIR-6236表达与高血糖和葡萄糖耐受不良呈负相关，与胰岛素敏感性呈正相关。一起,我们的发现将miR-6236确立为ATM分泌的miRNA,可增强脂肪细胞胰岛素信号传导并防止肥胖期间的代谢功能障碍.
