Prolonged therapeutic effects of exosomes from light treated-adipose-derived stem cells on obesity-associated insulin resistance

Background: Obesity induces adipose tissue chronic inflammation resulting in insulin resistance and metabolic disorders. With light activation, we recently showed that in situ transplantation of photoactivated adipose-derived stem cells (ASCs) improves glucose metabolism by suppressing adipose tissue macrophages in obese mice. Still, the mechanisms have not been thoroughly investigated. Methods: Cultured ASCs were subjected to light treatment, and exosomes (Exos) were subsequently harvested and injected intraperitoneally into HFD mice. High-throughput miRNA sequencing was performed to detect the miRNA profiles of light-activated ASCs-Exos. The roles of miRNA and target gene were predicted and analyzed in vitro or in vivo by dual-luciferase reporter gene assay, specific miRNA mimic, miRNA inhibitor, and siRNA. Results: We showed that light-activated ASCs produce miRNA-containing exosomes (Exos), which significantly prolonged therapeutic effects on the improvement of obesity-associated insulin tolerance when injected intraperitoneally into obese mice. Mechanistically, light-activated ASCs-Exos shift M1 macrophages toward the M2 via miR-3572-5p–mediated targeting of ELVAL1 in vitro and in vivo. Moreover, miR-3572-5p inhibitor delivery significantly modulated insulin sensitivity and macrophage phenotype. Conclusions: These data suggest that light activation is a simple and effective method for generating the functionality of ASCs-Exos, and miR-3572-5p could be a new therapeutic target of adipose tissue inflammation for insulin resistance. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.