Brown adipocyte-derived exosomes in type 2 diabetes mellitus impair endothelial function via regulating intracellular calcium cycle.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Atherosclerosis is a leading cause of macrovascular complications in type 2 diabetes mellitus (T2DM). Lipid metabolism disorders in T2DM alter exosomal cargos, affecting vascular endothelial cells and impairing vascular endothelium-dependent relaxation. Objective This study investigates the link between T2DM and atherosclerosis, focusing on adipose tissue-derived exosomes (AT-Exosomes) as key pathogenic factors in T2DM. Methods AT-exosomes derived from diabetic (C57BLKS-Lepr db/db ) and non-diabetic (C57BLKS-Lepr db/+ ) mice were co-cultured with vascular aorta to evaluate pathogenicity. RNA screening in mouse aortic endothelial cells (MAECs) identified differential genes impacted by T2DM brown adipose tissue (BAT)-derived vs. healthy BAT-derived exosomes. Result BAT-derived exosomes significantly disrupted endothelium function compared to white adipose tissue (WAT)-derived exosomes. Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) gene expression in MAECs was significantly reduced in diabetic mice. Functional studies revealed that ITPR3 positively regulates the Ca 2+ /CAMKII/eNOS signaling pathway to inhibit nitric oxide (NO) release, impairing endothelial relaxation. Conclusion BAT-derived exosomes in T2DM reduce ITPR3 expression in endothelial cells, lowering intracellular Ca 2+ and NO production, thereby contributing to vascular endothelium-dependent relaxati

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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