Cold exposure (CE) could increase insulin sensitivity in high-fat-diet (HFD) mice, relying on adipose tissue Ucp1-induced heat release and macrophage M2 polarization. The function of thermogenic macrophages, a new subtype of macrophages that we have recently identified, has not been clearly investigated in insulin sensitivity caused by cold exposure. We used HFD wild-type (WT) mice and Ucp1 conditionally knockout in macrophages (Ucp1-cKO) mice which housed in 16°C for 2 mouths, and detected their physiological characteristics, metabolic cage, and proteome profiles of different adipose tissues based on mass spectrometry. We found that the body weights of Ucp1-cKO mice were significantly higher than that of WT mice, and the oxygen consumption and heat release were reduced in Ucp1-cKO mice, which demonstrated a weaker metabolic activity of Ucp1-cKO mice upon CE. The glucose and insulin tolerance tests indicated that Ucp1 deletion in macrophages abated insulin sensitivity caused by CE. In addition, thermogenic proteins, represented by Ucp1, were inhibited in subcutaneous adipose tissue of Ucp1-cKO mice, suggesting that the loss of macrophage thermogenesis could reduce the thermogenesis metabolism of the whole sWAT. The adipocytes in sWAT were malformed and hypertrophied, and the cytokines secreted by macrophages were no difference between each other. These conclusions confirm the important role of thermogenic macrophages in promoting adipose tissue thermogenesis and insulin resistance in HFD mice, and provide a potential strategy for cell therapies in diabetes treatment.
L. Sun: None.
