miR-210-3p–enriched EVs of obese ATMs promote glucose intolerance and insulin resistance in vivo.A, schematic diagram showing standard diet–fed C57BL/6 mice administered with EVs isolated from Dicer-silenced macrophages transfected with control mimic and miR-210-3p mimic via an intravenous route with a regular interval for 21 days before termination of the experiment. B–D, glucose tolerance test (GTT) (B), insulin tolerance test (ITT) (C), and HOMA-IR (D) analyses were performed in StndD fed–mice injected with EVs isolated from Dicer-silenced macrophage transfected with control mimic LNA or miR-210-3p mimic LNA (n = 4). ∗p < 0.05, ∗∗p < 0.01, ns-non-significant by two-way ANOVA and ∗∗p < 0.01 unpaired Student’s t test. E–G, GLUT4 mRNA expression analyses (E), western blotting (F), and quantification analyses (G) in visceral adipose tissue (AT), Liver, and skeletal muscle (SM) in standard diet–fed C57BL/6 mice administered with Dicer-silenced macrophage exosomes having control mimic LNA or miR-210-3p mimic LNA via the intravenous route in regular intervals for 21 days (n = 4), ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001 by two-way ANOVA. H, schematic diagram showing control mimic or miR-210-3p mimic LNA intravenous injection in regular intervals for 21 days in C57BL/6 mice. I and J, glucose tolerance test (I) and insulin tolerance test (J) were performed in standard diet–fed mice administered with control mimic LNA and miR-210-3p mimic LNA with each 3 days interval in the period of 21 days, (n = 4), ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ns non-significant by two-way ANOVA. K–M, qRT-PCR analyses (K), immunoblotting (L), and quantification analyses (M) of GLUT4, in standard diet–fed C57BL/6 mice injected with control mimic LNA or miR-210-3p mimic LNA via the intravenous route in regular intervals for 21 days, (n = 4), ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001 two-way ANOVA. Data are expressed as means ± SD; n = 3 to 4. ATM, adipose tissue macrophage; EV, extracellular vesicle; HOMA-IR, homeostatic model assessment for insulin resistance; LNA, locked nucleic acid; StndD, standard diet.