Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Sci Rep. 2019 Jan 22;9(1):279. doi: 10.1038/s41598-018-36651-2.
We have previously shown that high fat diet (HFD) for 2 weeks increases airway hyperresponsiveness (AHR) to methacholine challenge in C57BL/6J mice in association with an increase in IL-1β levels in lung tissue. We hypothesize that obesity increases AHR via the IL-1β mechanism, which can be prevented by caloric restriction and IL-1β blockade. In this study, we fed C57BL/6J mice for 8 weeks with several hypercaloric diets, including HFD, HFD supplemented with fructose, high trans-fat diet (HTFD) supplemented with fructose, either ad libitum or restricting their food intake to match body weight to the mice on a chow diet (CD). We also assessed the effect of the IL-1β receptor blocker anakinra. All mice showed the same total respiratory resistance at baseline. All obese mice showed higher AHR at 30 mg/ml of methacholine compared to CD and food restricted groups, regardless of the diet. Obese mice showed significant increases in lung IL-1 β mRNA expression, but not the protein, compared to CD and food restricted mice. Anakinra abolished an increase in AHR. We conclude that obesity leads to the airway hyperresponsiveness preventable by caloric restriction and IL-1β blockade.
我们之前的研究表明，高脂肪饮食（HFD）喂养 2 周会导致 C57BL/6J 小鼠气道对乙酰甲胆碱激发的反应性增加，同时肺组织中白细胞介素-1β（IL-1β）水平升高。我们假设肥胖通过 IL-1β机制增加气道高反应性，而热量限制和 IL-1β 阻断可以预防这种情况。在这项研究中，我们用几种高热量饮食（包括 HFD、HFD 加果糖、高反式脂肪饮食（HTFD）加果糖）喂养 C57BL/6J 小鼠 8 周，其中一些自由进食，一些限制饮食使其体重与进食标准饲料（CD）的小鼠相当。我们还评估了 IL-1β 受体阻滞剂 anakinra 的作用。所有小鼠在基线时的总呼吸阻力相同。与 CD 和食物限制组相比，所有肥胖小鼠在 30mg/ml 乙酰甲胆碱时均表现出更高的气道高反应性，无论饮食如何。与 CD 和食物限制组相比，肥胖组小鼠肺组织中 IL-1β mRNA 表达显著增加，但蛋白水平没有增加。Anakinra 消除了气道高反应性的增加。我们的结论是，肥胖导致气道高反应性，这种高反应性可以通过热量限制和 IL-1β 阻断来预防。
