2023-07-25 カリフォルニア大学リバーサイド校(UCR)
◆RELMalphaは免疫応答を制御し、メスのマウスでは特に肥満と炎症を防ぐ「RELMalpha-好酸球-マクロファージ軸」が機能していることが示されました。この発見は、肥満と炎症に対する新しい治療法の可能性を示唆しています。
<関連情報>
- https://news.ucr.edu/articles/2023/07/25/protein-found-protect-females-against-obesity
- https://elifesciences.org/articles/86001
肥満の性的二型は脂肪マクロファージと好酸球のRELMα制御に支配される Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils
Jiang Li,Rebecca E Ruggiero-Ruff,Yuxin He,Xinru Qiu,Nancy Lainez,Pedro Villa,Adam Godzik,Djurdjica Coss,Meera G Nair
eLife Published:May 10, 2023
DOI:https://doi.org/10.7554/eLife.86001
Abstract
Obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Sex differences in immune cell activation drive obesity-mediated pathologies where males are more susceptible to obesity comorbidities and exacerbated inflammation. Here, we demonstrate that the macrophage-secreted protein RELMα critically protects females against high-fat diet (HFD)-induced obesity. Compared to male mice, serum RELMα levels were higher in both control and HFD-fed females and correlated with frequency of adipose macrophages and eosinophils. RELMα-deficient females gained more weight and had proinflammatory macrophage accumulation and eosinophil loss in the adipose stromal vascular fraction (SVF), while RELMα treatment or eosinophil transfer rescued this phenotype. Single-cell RNA-sequencing of the adipose SVF was performed and identified sex and RELMα-dependent changes. Genes involved in oxygen sensing and iron homeostasis, including hemoglobin and lncRNA Gm47283/Gm21887, correlated with increased obesity, while eosinophil chemotaxis and response to amyloid-beta were protective. Monocyte-to-macrophage transition was also dysregulated in RELMα-deficient animals. Collectively, these studies implicate a RELMα–macrophage–eosinophil axis in sex-specific protection against obesity and uncover new therapeutic targets for obesity.
Editor’s evaluation
In this study, Li and al describe valuable insights into mechanisms underlying sex-differences for diet-induced obesity in mice, demonstrating a role for macrophage-derived RELMa secretion in determining female-specific obesity protection. They provide evidence for the impact of RELMa signaling in eosinophil recruitment for diet-induced obesity protection in female mice. Single-cell RNA-seq analysis of the stromal vascular fraction of control and RELMa deficient animals were used to investigate molecular mechanisms underlying the protection. The conclusion of these findings provides evidence supporting dysregulation of cell differentiation pathways.
