JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation
Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism and Diabetes
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Endocrinology | Immunity | Molecular Biology
The cJun NH(2)-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. We report that feeding a high-fat diet to control and JNK-deficient mice caused similar obesity, but only mice with JNK-deficient macrophages remained insulin-sensitive. The protection of mice with macrophage-specific JNK deficiency against insulin resistance was associated with reduced tissue infiltration by macrophages. Immunophenotyping demonstrated that JNK was required for pro-inflammatory macrophage polarization. These studies demonstrate that JNK in macrophages is required for the establishment of obesity-induced insulin resistance and inflammation.
DOI of Published Version
Science. 2013 Jan 11;339(6116):218-22. doi: 10.1126/science.1227568. Link to article on publisher's site
Science (New York, N.Y.)
Han MS, Jung D, Morel C, Lakhani SA, Kim JK, Flavell RA, Davis RJ. (2013). JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1126/science.1227568. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/207