Emodin inhibits lipid accumulation and inflammation in adipose tissue of high‐fat diet‐fed mice by inducing M2 polarization of adipose tissue macrophages

Abstract

Adipose tissue macrophages (ATMs) represent the most abundant leukocytes in adipose tissue (AT). An increase in number and a phenotypical switch of ATMs during the development of obesity contribute to chronic inflammation and metabolic disorders, which have been regarded as potential therapeutic targets to restore AT homeostasis. Emodin has been shown to exert strong anti‐inflammatory 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‐fat diet (HFD)‐induced 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‐fed 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‐treated ATMs. We further identified that TREM2 was the most dramatically upregulated molecule by emodin and emodin‐induced 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.

Advances in the study of emodin: an update on pharmacological properties and mechanistic basis

“…However, the promotive effects of emodin on M2 macrophage activation were the primary mechanism underlying its therapeutic effects against asthma. Most recent evidence also reported opposite results that emodin (80 mg/kg) dramatically upregulated trigger receptor expressed on myeloid cells 2 to promote macrophage polarization, thus inhibiting metabolic diseases like obesity and in HFD-mice model [ 218 ]. Further studies are required to address these critical issues.…”

Effects of Anthraquinones on Immune Responses and Inflammatory Diseases

“…In high-fat diet (HFD)-induced obese mice, emodin significantly inhibited lipid accumulation, reduced glucose and insulin levels, ameliorated serum lipid profiles and the local and systemic inflammation. The percentage M2 macrophage was greatly increased by emodin in adipose tissue [120]. In a high-fat diet plus streptozotocin-induced T2D rat model, emodin ameliorated hyperglycemia, dyslipidemia, and glucose metabolism, which was controlled by SMAD7 regulated by miR-20b [121].…”

Natural compounds as obesity pharmacotherapies

“…HFD‐fed mice gain 34.0% less BW after emodin treatment at 80 mg/kg/day (i.g.) for 12 weeks (Yu et al, 2021). This effect is similarly observed in rats, where HFD‐fed rats gained 4.3%–10.4% less BW when emodin treatment at 20–80 mg/kg/day (i.g.)…”