The enhancement of chronic inflammation via interorgan communication like liver-adipose tissue is one of the pathological bases for the development of obesity. Although small extracellular vesicles (sEVs) are suggested to play a critical role in intercellular communications and glucose intolerance in obese and diabetic conditions, the exact target tissue/cells for hepatocyte-derived sEVs (HsEVs) in vivo and their contribution to chronic inflammation are not clear.
Therefore, we have generated a new mouse model to track HsEVs by scarlet, red fluorescent protein, in vivo.
We observed high numbers of scarlet-positive (Sc+) CD45-positive cells without expressing scarlet mRNA in the pancreas, and visceral adipose tissue (eWAT), suggesting Sc+ HsEVs-recipient cells are contained in these tissues. The scRNA-seq determined that macrophages/monocytes are the major HsEVs-recipient cell types. High-fat diet (HFD) increased mRNA expression for sEV biogenesis in the liver and Sc+ HsEVs ratio in the serum in mice. Sc+ macrophages exhibited higher levels of TNFa compared to scarlet-negative macrophages, and this level in the Sc+ macrophage was further enhanced in the HFD condition.
These data suggest that the hepatocytes in obesity are involved in generating pro-inflammatory sEVs, which may contribute to macrophage activation in the eWAT.