The deficiency of macrophage erythropoietin signaling contributes to delayed acute inflammation resolution in diet-induced obese mice |
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Authors: | Bangwei Luo Zhishang Wang Zhiyuan Zhang Zigang Shen Zhiren Zhang |
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Affiliation: | 1. Discipline Integrated Chinese and Western Medicine, School of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China;2. Institute of Immunology, Army Medical University, 30 Gaotanyan Main Street, Chongqing 400038, China;3. Department of Pathology, Nanjing Medical University, Hanzhong Road 140, Nanjing 210029, China |
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Abstract: | Obesity has been linked with altered acute inflammation resolution which contributes to obesity-related clinical complications; however, the mechanisms that contribute to obesity-related unresolved inflammation are not fully known. Here we demonstrated that the deficiency of macrophage erythropoietin (EPO) signaling contributed to delayed acute inflammation resolution in diet-induced obese mice. In zymosan-induced acute peritonitis, in line with the delayed resolution of inflammation, the induction of macrophage EPO signaling was significantly reduced in obese mice relative to normal mice. Exogenous EPO induced macrophage EPO signaling and promoted acute inflammation resolution in obese mice. Efferocytosis of apoptotic cells by macrophages which is central in inflammation resolution was impaired in obese mice and restored by exogenous EPO. Mechanistically, macrophage peroxisome proliferator-activated receptor-γ (PPARγ) was greatly reduced in obese mice and EPO increased macrophage PPARγ to promote efferocytosis in obese mice. Together, our results identify an important mechanism underlying aberrant acute inflammation resolution in obesity, with important implications for regulating unresolved acute inflammation and normalizing macrophage defects in obese and diabetic individuals. |
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Keywords: | Inflammation resolution Erythropoietin Obesity Macrophage |
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