miR-210-3pPromotes Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance by Targeting SOCS1-Mediated NF-κB Pathway

• DOI: 10.2337/db22-0284
• Publication Date: 2022-12-05T16:16:27Z
• Authors: Debarun Patra; Soumyajit Roy; Leena Arora; Shaheen Wasil Kabeer; Satpal Singh; Upalabdha Dey; Dipanjan Banerjee; Archana Sinha; Suman Dasgupta; Kulbhushan Tikoo; Aditya Kumar; Durba Pal
• Keywords: Proinflammatory cytokine; Adipose tissue macrophages; Macrophage polarization

Under the condition of chronic obesity, an increased level free fatty acids along with low oxygen tension in adipose tissue creates a pathophysiological microenvironment (ATenv), leading to impairment adipocyte function and insulin resistance. Here, we found synergistic effect hypoxia lipid (H + L) surge fostering macrophage (ATM) inflammation polarization. ATenv significantly miR-210-3p expression ATMs which promotes NF-κB activation–dependent proinflammatory cytokine downregulation anti-inflammatory expression. Interestingly, delivery mimic absence H L co-stimulation, while inhibitor notably compromised L–induced through production suppressor signaling 1 (SOCS1), negative regulator inflammatory pathway. Mechanistically, miR-210 directly binds 3′-UTR SOCS1 mRNA silences its expression, thus preventing proteasomal degradation p65. Direct anti–miR-210-3p LNA markedly rescued mice from obesity-induced Thus, inhibition could serve as novel therapeutic strategy for managing type 2 diabetes.