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An increase in number and a phenotypical switch of ATMs during the development of obesity contribute\u00a0to\u00a0chronic\u00a0inflammation\u00a0and metabolic disorders, which have been regarded as potential therapeutic targets to restore AT homeostasis. Emodin has been shown to exert strong anti\u2010inflammatory property via acting on macrophages in a range of disease models. However, whether emodin exerts a beneficial effect on obesity via modulating ATMs has not been reported. In high\u2010fat diet (HFD)\u2010induced obese mice, emodin significantly inhibited the increase of body weight and lipid accumulation in ATs. Emodin apparently reduced glucose and insulin levels and ameliorated serum lipid profiles in HFD\u2010fed mice. Moreover, the local and systemic inflammation was dramatically alleviated by emodin. We next discovered that M2 macrophage percentage was greatly increased by emodin although total ATMs was not altered, which resulted in a net increase of M2 macrophages in AT. In vitro studies confirmed that emodin promoted the polarization of macrophages towards M2. Gene ontology (GO) analysis showed that myeloid leukocyte differentiation and activation were among the most significant biological processes in emodin\u2010treated ATMs. We further identified that TREM2 was the most dramatically upregulated molecule by emodin and emodin\u2010induced M2 macrophage polarization was dependent on TREM2. Furthermore, silencing TREM2 apparently abrogated the effect of emodin on AT inflammation and adipogenesis. We, for the first time, disclosed that emodin inhibited obesity by promoting M2 macrophage polarization via TREM2, suggesting that emodin may be explored as a clinical and translational candidate in preventing obesity and its related metabolic diseases.<\/jats:p>","DOI":"10.1096\/fj.202100157rr","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:25:57Z","timestamp":1623371157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Emodin inhibits lipid accumulation and inflammation in adipose tissue of high\u2010fat diet\u2010fed mice by inducing M2 polarization of adipose tissue macrophages"],"prefix":"10.1096","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4192-4918","authenticated-orcid":false,"given":"Fang","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene &amp; Department of Health Education and Health 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