부산대학교 도서관

Objective The cJun NH2-terminal kinase (JNK) signaling pathway contributes to inflammation and plays a key role in the metabolic response to obesity, including insulin resistance. Macrophages are implicated in this process. To test the role of JNK, we established mice with selective JNK-deficiency in macrophages. Methods We investigated glucose metabolism and insulin sensitivity on macrophage-specific JNK-deficiency (MKO) mice after feeding a high fat diet. The number and the expression of marker genes for M1 and M2 macrophages from adipose tissue and polarization of macrophage in vitro were analyzed using flow cytometry and quantative PCR. Results Macrophage JNK-deficiency mice exhibit improved insulin and glucose tolerance, hyperglycemia and hyperinsulinemia compared with HFD-fed MWT mice. Futhermore, HFD-fed MKO mice remained insulin sensitive. Flow cytometry analysis demonstrated that macrophage JNK-deficiency prevented the accumulation of ATM and ATM expressing surface markers (F4/80+ CD11c+ CD206-) associated with M1 polarization in adipose tissue of HFD-fed mice. Macrophage JNK-deficiency decreased the expression of ATM marker genes (Cd68 & F4/80) and M1 marker genes and increased M2 marker genes in adipose tissue of HFD-fed mice. We also found that macrophage JNK-deficiency caused decreased expression of M1 marker genes in IFN-g or LPS stimulated macrophages in vitro. Conclusion JNK-dependent M1 polarization of tissue macrophages may also contribute to the inflammation associated with insulin resistance caused by diet-induced obesity. Indeed, JNK in macrophages is required for the accumulation of M1 tissue macrophages and insulin resistance caused by diet-induced obesity.