Fig. 8

Schematic representation of the mechanisms of GDM EVs-derived miR-1299 induction of hepatic insulin resistance. In women with GDM, the levels of circulating EVs were elevated and miR-1299 was highly expressed in these EVs. Circulating GDM EVs were absorbed by hepatocytes, leading to an increase in the level of miR-1299 within these cells. Then, miR-1299 binding to the 3ʹUTR of STAT3 mRNA resulted in STAT3 translational arrest which consequently reduced the expression of FAM3A. The decreased levels of STAT3 and FAM3A can potentially affect mitochondrial function by slowing down TCA cycle flux and mitochondrial respiration, while increasing oxidative stress. Therefore, elevated miR-1299 in circulating GDM EVs is proposed to induce hepatic insulin resistance through impaired mitochondrial function via inhibiting the STAT3/FAM3A axis