Impact of controlled high-sucrose and high-fat diets on eosinophil recruitment and cytokine content in allergen-challenged mice.
Impact of controlled high-sucrose and high-fat diets on eosinophil recruitment and cytokine content in allergen-challenged mice.
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DOI：
10.1371/journal.pone.0255997
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Rosenberg HF
中科院分区：
文献类型：
--
作者：
Percopo CM;McCullough M;Limkar AR;Druey KM;Rosenberg HF
尽管人们一直关注饮食在健康和疾病中的作用，但我们在细胞和分子水平上对这些概念的理解有限。虽然肥胖已被明确认为是导致代谢综合征和成人哮喘发病机制的原因，但最近的证据表明，仅高糖摄入就与儿童期哮喘发病风险增加有关。在这项研究中，我们研究了饮食在小鼠过敏性气道炎症模型中的影响，特别关注嗜酸性粒细胞。正如预期的那样，雄性C57 BL/6小鼠在高热量，高脂肪饮食中体重增加。然而，小鼠在等热量的高蔗糖饮食中也增加了体重。高脂饮食组小鼠的血清和气道中检测到瘦素水平升高，但高糖饮食组小鼠的血清和气道中检测不到瘦素水平升高。我们发现，无论是野生型还是瘦素缺陷型ob/ob小鼠，单独饮食对气道中嗜酸性粒细胞数量没有影响，也没有影响它们对过敏原（链格孢菌）攻击的反应。然而，支气管肺泡灌洗液和嗜酸性粒细胞从过敏原激发小鼠肺组织中分离出的细胞因子含量表现出深刻的饮食依赖性差异。同样，虽然所有野生型小鼠对过敏原激发的反应都是乙酰甲胆碱依赖性总气道阻力（Rrs）显著增加，但维持等热量高蔗糖（但不是高热量/高脂肪）饮食的小鼠的气道阻力显著超过维持基础饮食的小鼠。总之，我们的研究结果表明，维持在等热量高蔗糖饮食的小鼠对过敏原激发有反应，BAL和嗜酸性粒细胞细胞因子含量均发生显著变化，Rrs显著增加。这些结果为进一步探索与高糖饮食相关的独特风险及其对过敏原相关呼吸功能障碍的影响提供了模型。
Despite an ongoing focus on the role of diet in health and disease, we have only a limited understanding of these concepts at the cellular and molecular levels. While obesity has been clearly recognized as contributing to metabolic syndrome and the pathogenesis of adult asthma, recent evidence has linked high sugar intake alone to an increased risk of developing asthma in childhood. In this study, we examined the impact of diet in a mouse model of allergic airways inflammation with a specific focus on eosinophils. As anticipated, male C57BL/6 mice gained weight on a high-calorie, high-fat diet. However, mice also gained weight on an isocaloric high-sucrose diet. Elevated levels of leptin were detected in the serum and airways of mice maintained on the high-fat, but not the high-sucrose diets. We found that diet alone had no impact on eosinophil numbers in the airways at baseline or their recruitment in response to allergen (Alternaria alternata) challenge in either wild-type or leptin-deficient ob/ob mice. However, both bronchoalveolar lavage fluid and eosinophils isolated from lung tissue of allergen-challenged mice exhibited profound diet-dependent differences in cytokine content. Similarly, while all wild-type mice responded to allergen challenge with significant increases in methacholine-dependent total airway resistance (Rrs), airway resistance in mice maintained on the isocaloric high-sucrose (but not the high-calorie/high-fat) diet significantly exceeded that of mice maintained on the basic diet. In summary, our findings revealed that mice maintained on an isocaloric high-sucrose diet responded to allergen challenge with significant changes in both BAL and eosinophil cytokine content together with significant increases in Rrs. These results provide a model for further exploration of the unique risks associated with a high-sugar diet and its impact on allergen-associated respiratory dysfunction.
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