Schuetz Lisa T, Duran Gayel, Baeten Paulien, Lintsen Daphne, Hermans Doryssa, Chenine Sarah, Verreycken Janne, Vanmierlo Tim, Wouters Kristiaan, Broux Bieke
Neuro-Immune Connections and Repair Lab, Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
CARIM-School of Cardiovascular Diseases, Maastricht University, Maastricht, Netherlands.
Biol Sex Differ. 2024 Dec 18;15(1):105. doi: 10.1186/s13293-024-00677-1.
Obesity is a growing pandemic that increases the risk for cardiovascular diseases, type 2 diabetes, and particularly in women also the risk of cancer and neurodegenerative disorders such as dementia and multiple sclerosis. Preclinical studies on obesity focus on male mice as they gain bodyweight faster and show a clear pro-inflammatory phenotype. Here, using male and female mice, we induced obesity by feeding a high fat diet (HFD), and compared adipose tissue (AT) inflammation at the same adiposity stage (% AT/bodyweight) between both sexes. Doing so, we identified that female mice show an increase in the number of pro-inflammatory immune cells in the visceral AT at a lower adiposity stage than male mice, but the effect of HFD is diminished with higher adiposity. Interestingly, only female mice showed an increase in immune cells in the subcutaneous AT after HFD feeding. Nonetheless, we found that pro-inflammatory cytokines in blood plasma mirror the inflammatory stage of the visceral AT in both male and female mice. Uniquely in male mice, myeloid cells in the visceral AT showed a higher inflammasome activation upon HFD. In summary, we showed that adiposity differentially affects immune cells in fat depots based on sex.
肥胖是一种日益流行的疾病，它会增加患心血管疾病、2型糖尿病的风险，尤其在女性中，还会增加患癌症和神经退行性疾病（如痴呆症和多发性硬化症）的风险。肥胖的临床前研究主要集中在雄性小鼠身上，因为它们体重增加更快，并且表现出明显的促炎表型。在这里，我们使用雄性和雌性小鼠，通过喂食高脂饮食（HFD）诱导肥胖，并比较了两性在相同肥胖阶段（脂肪组织占体重的百分比）时脂肪组织（AT）的炎症情况。通过这样做，我们发现雌性小鼠在内脏脂肪组织中促炎免疫细胞数量的增加发生在比雄性小鼠更低的肥胖阶段，但高脂饮食的影响在更高肥胖程度时会减弱。有趣的是，只有雌性小鼠在喂食高脂饮食后皮下脂肪组织中的免疫细胞数量增加。尽管如此，我们发现血浆中的促炎细胞因子反映了雄性和雌性小鼠内脏脂肪组织的炎症阶段。在内脏脂肪组织中，髓样细胞在雄性小鼠中对高脂饮食表现出更高的炎性小体激活，这一点是雄性小鼠所特有的。总之，我们表明肥胖根据性别对脂肪库中的免疫细胞有不同影响。
