JNK Expression by Macrophages Promotes Obesity-Induced Insulin Resistance and Inflammation

Science  11 Jan 2013:
Vol. 339, Issue 6116, pp. 218-222
DOI: 10.1126/science.1227568

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Macrophage JNK in Metabolic Disease

Inflammation is thought to be an important driver of diet-induced obesity and insulin resistance. Proinflammatory, M1 phenotype macrophages and the c-jun NH2 terminal kinases (JNK) are central players in this process. But whether JNK expression is specifically required inside macrophages is unclear. In mice containing a macrophage-specific deletion in both Jnk1 and Jnk2, Han et al. (p. 218, published online 6 December; see the Perspective by Ferrante Jr.) found that the mice were protected against many of the diet-induced metabolic changes, including insulin resistance, despite similar weight gain as control mice on a high-fat diet. This protection was associated with a decrease in the presence of M1 macrophages in adipose tissue.


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. 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.

  • * Present address: Department of Pediatrics, Sanford University School of Medicine, Sioux Falls, SD 57117, USA.

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