Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils
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-s...
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| Format: | Article |
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eLife Sciences Publications Ltd
2023-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/86001 |
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| author | Jiang Li Rebecca E Ruggiero-Ruff Yuxin He Xinru Qiu Nancy Lainez Pedro Villa Adam Godzik Djurdjica Coss Meera G Nair |
| author_facet | Jiang Li Rebecca E Ruggiero-Ruff Yuxin He Xinru Qiu Nancy Lainez Pedro Villa Adam Godzik Djurdjica Coss Meera G Nair |
| author_sort | Jiang Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T13:25:17Z |
| format | Article |
| id | doaj.art-683e0bea8a2a425281f150b27e0db2da |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T13:25:17Z |
| publishDate | 2023-05-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-683e0bea8a2a425281f150b27e0db2da2023-05-10T12:16:47ZengeLife Sciences Publications LtdeLife2050-084X2023-05-011210.7554/eLife.86001Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophilsJiang Li0Rebecca E Ruggiero-Ruff1https://orcid.org/0000-0001-9093-0233Yuxin He2Xinru Qiu3https://orcid.org/0000-0003-1391-252XNancy Lainez4https://orcid.org/0000-0002-3191-9023Pedro Villa5https://orcid.org/0000-0002-5245-4130Adam Godzik6https://orcid.org/0000-0002-2425-852XDjurdjica Coss7https://orcid.org/0000-0003-0692-1612Meera G Nair8https://orcid.org/0000-0002-1807-5161Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, United StatesDivision of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, United StatesDivision of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, United StatesGraduate Program in Genetics, Genomics and Bioinformatics, University of California Riverside, Riverside, United StatesDivision of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, United StatesDivision of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, United StatesDivision of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, United StatesDivision of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, United StatesDivision of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, United StatesObesity 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.https://elifesciences.org/articles/86001macrophageeosinophilobesitysexual dimorphismadiposeRELMα |
| spellingShingle | Jiang Li Rebecca E Ruggiero-Ruff Yuxin He Xinru Qiu Nancy Lainez Pedro Villa Adam Godzik Djurdjica Coss Meera G Nair Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils eLife macrophage eosinophil obesity sexual dimorphism adipose RELMα |
| title | Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils |
| title_full | Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils |
| title_fullStr | Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils |
| title_full_unstemmed | Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils |
| title_short | Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils |
| title_sort | sexual dimorphism in obesity is governed by relmα regulation of adipose macrophages and eosinophils |
| topic | macrophage eosinophil obesity sexual dimorphism adipose RELMα |
| url | https://elifesciences.org/articles/86001 |
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