生酮饮食在变应性气道炎症小鼠模型中的性别特异性抗炎作用

Sex-Specific Anti-Inflammatory Effects of a Ketogenic Diet in a Mouse Model of Allergic Airway Inflammation.

作者信息

Ekpruke Carolyn D, Borges-Sosa Omar, Hassel Christiane A, Rousselle Dustin, Dinwiddie Lyidia, Babayev Maksat, Bakare Ahmed, Silveyra Patricia

机构信息

Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, IN 47405, USA.

Flow Cytometry Core Facility, Indiana University, Bloomington, IN 47405, USA.

出版信息

Int J Mol Sci. 2025 Mar 26;26(7):3046. doi: 10.3390/ijms26073046.

Abstract

Asthma, a chronic inflammatory airway disease, leads to airflow obstruction and exhibits sex differences in prevalence and severity. Immunomodulatory diets, such as the ketogenic diet (high fat, low carbohydrate, moderate protein), may offer complementary benefits in managing airway inflammation. While anti-inflammatory effects of ketogenic diets are documented in cardiovascular diseases, their impact on asthma, especially regarding sex-specific differences, remains unexplored. Few studies on diet and asthma have considered sex as a biological factor. To test the hypothesis that a ketogenic diet affects airway inflammation in a sex-specific manner, we used a mouse allergic airway inflammation model. Male and female C57BL/6J mice (3-4 weeks old, = 5-6/group) were fed a ketogenic diet or normal chow for 12 weeks. From weeks 7 to 12, mice were challenged intranasally with house dust mite allergens (HDM) 5 days/week to induce airway inflammation. Lung tissue was analyzed 72 h post-exposure using flow cytometry to assess immune cell populations, and data were analyzed with two-way ANOVA. The ketogenic diet increased body weight in allergen-exposed mice, with a greater effect in males than females ( = 0.0512). Significant sex-diet interactions were noted for alveolar macrophages, CD103, CD11B, and plasmacytoid dendritic cells ( < 0.05). Eosinophil reductions were observed in males but not females on the ketogenic diet. The diet also increased NKT cells and decreased NK cells in males but not females ( < 0.001). These findings highlight sex-specific effects of ketogenic diets on lung immune responses, with stronger impacts in males.

摘要

哮喘是一种慢性炎症性气道疾病,会导致气流阻塞,且在患病率和严重程度上存在性别差异。免疫调节饮食,如生酮饮食(高脂肪、低碳水化合物、适量蛋白质),可能在控制气道炎症方面提供辅助益处。虽然生酮饮食的抗炎作用在心血管疾病中已有记载,但其对哮喘的影响,尤其是关于性别特异性差异,仍未得到探索。很少有关于饮食与哮喘的研究将性别视为一个生物学因素。为了验证生酮饮食以性别特异性方式影响气道炎症这一假设,我们使用了小鼠过敏性气道炎症模型。将雄性和雌性C57BL/6J小鼠(3 - 4周龄,每组n = 5 - 6只)喂食生酮饮食或正常食物12周。从第7周到第12周,每周5天经鼻用屋尘螨过敏原(HDM)攻击小鼠以诱导气道炎症。暴露72小时后,使用流式细胞术分析肺组织以评估免疫细胞群体,并采用双向方差分析对数据进行分析。生酮饮食使暴露于过敏原的小鼠体重增加,对雄性的影响大于雌性(P = 0.0512)。在肺泡巨噬细胞、CD103、CD11B和浆细胞样树突状细胞方面观察到显著的性别 - 饮食相互作用(P < 0.05)。在喂食生酮饮食的雄性小鼠中观察到嗜酸性粒细胞减少,而雌性小鼠未出现。该饮食还使雄性小鼠的NKT细胞增加,NK细胞减少,而雌性小鼠未出现这种情况(P < 0.001)。这些发现突出了生酮饮食对肺部免疫反应的性别特异性影响,对雄性的影响更强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0554/11989016/8c2b984ced7d/ijms-26-03046-g001.jpg

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