| First Author | Luan D | Year | 2023 |
| Journal | Diabetes | Volume | 72 |
| Issue | 3 | Pages | 367-374 |
| PubMed ID | 36449000 | Mgi Jnum | J:347698 |
| Mgi Id | MGI:7439004 | Doi | 10.2337/db22-0444 |
| Citation | Luan D, et al. (2023) Adipocyte-Secreted IL-6 Sensitizes Macrophages to IL-4 Signaling. Diabetes 72(3):367-374 |
| abstractText | Complex bidirectional cross talk between adipocytes and adipose tissue immune cells plays an important role in regulating adipose function, inflammation, and insulin responsiveness. Adipocytes secrete the pleiotropic cytokine IL-6 in response to both inflammatory and catabolic stimuli. Previous studies have suggested that IL-6 secretion from adipocytes in obesity may promote adipose tissue inflammation. Here, we investigated catabolic stimulation of adipocyte IL-6 secretion and its impact on adipose tissue immune cells. In obesity, catecholamine resistance reduces cAMP-driven adipocyte IL-6 secretion in response to catabolic signals. By restoring adipocyte catecholamine sensitivity in obese adipocytes, amlexanox stimulates adipocyte-specific IL-6 secretion. We report that in this context, adipocyte-secreted IL-6 activates local macrophage STAT3 to promote Il4ra expression, thereby sensitizing them to IL-4 signaling and promoting an anti-inflammatory gene expression pattern. Supporting a paracrine adipocyte to macrophage mechanism, these effects could be recapitulated using adipocyte conditioned media to pretreat bone marrow-derived macrophages prior to polarization with IL-4. The effects of IL-6 signaling in adipose tissue are complex and context specific. These results suggest that cAMP-driven IL-6 secretion from adipocytes sensitizes adipose tissue macrophages to IL-4 signaling. |
