Exosome miR-152-3p derived from small intestinal epithelium modulates aging process in adipocytes.

Exosomes play a crucial role in facilitating intracellular communication between cells and tissues. The small intestine epithelium secretes exosomes, which is involved in various physiologic and pathologic processes. In this study, we investigated the effects of exosomal miR-152-3p derived from small intestinal epithelium on the aging process of adipocytes and its potential downstream mechanism. The exosomes derived from small intestinal epithelial cells were identified and characterized by TEM, NTA, and Western blot (WB). CCK-8 assay demonstrated the concentration-dependently increased 3T3-L1 cell viability by exosomes. PCR, Mito-Tracker red and DCFH-DA staining demonstrated the increased mtDNA content, mitochondrial activity, and the declined ROS content in 3T3-L1 adipocytes co-cultured with young exosomes. WB, PCR, β-galactosidase staining and ELISA demonstrated that the senescence was suppressed, uncoupling protein 1 (UCP1) and PPARgamma coactivator 1-alpha (PGC-1α) expression were upregulated, the levels of proinflammatory tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were decreased in 3T3-L1 adipocytes co-cultured with young exosomes. Luciferase reporter assay determined the binding between miR-152-3p and PGC-1α. WB and PCR manifested that miR-152-3p was lowly expressed in young exosomes and miR-152-3p could decrease PGC-1α expression and increase the expression of senescence-related genes. Moreover, ITT and GTT and H&E staining in in vivo elderly mouse model demonstrated that miR-152-3p inhibitor decreased visceral fat, improved glucose tolerance and insulin sensitivity and inhibited aging. WB and PCR suggested that miR-152-3p inhibitor enhanced PGC-1α expression, suppressed the expression of senescence-related genes and proinflammatory factors in vivo. In summary, intestinal exosomes affect the browning function of adipocytes through miR-152-3p, modulating the aging process.