Bone marrow mesenchymal stem cell‐derived exosomes reduce insulin resistance and obesity in mice via the PI3K/AKT signaling pathway

Obesity is a common chronic metabolic disease that induces chronic systemic inflammation in the body, eventually leading to related complications such as insulin resistance (IR), type 2 diabetes mellitus, and metabolic syndromes such as cardiovascular disease. Exosomes transfer bioactive substances to neighboring or distal cells through autosomal, paracrine, or distant secretion, regulating the gene and protein expression levels of receptor cells. In this study, we investigated the effect of mouse bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) on high-fat diet obese mice and mature 3T3-L1 adipocyte models of IR. BMSC-Exo treatment of obese mice promoted their metabolic homeostasis, including reduction of obesity, inhibition of M1-type proinflammatory factor expression, and improvement of insulin sensitivity. In vitro analysis revealed that BMSC-Exos improved IR and lipid droplet accumulation in mature 3T3-L1 adipocytes treated with palmitate (PA). Mechanistically, BMSC-Exos cause increased glucose uptake and improved IR in high-fat chow-fed mice and PA-acting 3T3-L1 adipocytes by activating the phosphoinositide 3-kinases/protein kinase B (PI3K/AKT) signaling pathway and upregulating glucose transporter protein 4 (GLUT4) expression. This study offers a new perspective for the development of treatments for IR in obese and diabetic patients.