肺部炎症对人和小鼠胰岛素抵抗的不同影响
2022/01/28
摘要
背景：在大多数国家，肥胖及其相关疾病和过敏的发病率正以惊人的速度上升。屋尘螨(HDM)具有高度过敏性，且暴露通常与城市久坐不动的室内生活方式有关，也会导致肥胖。
目的：本研究的目的是研究肺部炎症对肥胖和血糖稳态的流行病学关联和生理影响。
方法：采用基于人群的KORA-FF4队列中2207名成年人的流行病学数据，检测哮喘和鼻炎与体重和胰岛素敏感性指标之间的相关性。为了获得对功能的了解，采用HDM 对C57BL/6J小鼠进行鼻腔内致敏和激发，同时采用低脂或高脂饲料喂养12周，随后对肺、肝和脂肪组织进行详细的代谢和生化表型分析。
结果：我们发现人类哮喘与胰岛素抵抗直接相关，而与体重无关。在小鼠中，肥胖和HDM诱导的肺部炎症共同发展缓解了肺部和脂肪组织的炎症，对体重几乎没有影响，但肠道微生物群的组成发生了微小的变化。暴露于HDM可改善糖耐量，减少了肝脂肪变性，增加能量消耗和基础代谢率。这些效应与独立于解偶联蛋白 1 的产热脂肪组织活性增加有关。
结论：哮喘与人类胰岛素抵抗有关，但由于能量消耗增加，脂肪炎症和肝脂肪变性减少，在小鼠中HDM激发导致葡萄糖稳态的相反作用。
Differential effects of lung inflammation on insulin resistance in humans and mice
Ruth Karlina, Claudia Flexeder, Stephanie Musiol, Madhumita Bhattacharyya, Evelyn Schneider, Irem Altun, Silvia Gschwendtner, Avidan U Neumann, Jana Nano, Michael Schloter, Annette Peters, Holger Schulz, Carsten B Schmidt-Weber, Marie Standl, Claudia Traidl-Hoffmann, Francesca Alessandrini, Siegfried Ussar
Abstract
BACKGROUND: The rates of obesity, its associated diseases, and allergies are raising at alarming rates in most countries. House dust mites (HDM) are highly allergenic and exposure often associates with an urban sedentary indoor lifestyle, also resulting in obesity.
OBJECTIVE：The aim of this study was to investigate the epidemiological association and physiological impact of lung inflammation on obesity and glucose homeostasis.
METHODS: Epidemiological data from 2,207 adults of the population-based KORA-FF4 cohort were used to test associations between asthma and rhinitis with metrics of body weight and insulin sensitivity. To obtain functional insights, C57BL/6J mice were intranasally sensitized and challenged with HDM and simultaneously fed with either low fat or high fat diet for 12 weeks followed by a detailed metabolic and biochemical phenotyping of the lung, liver and adipose tissues.
RESULTS: We found a direct association of asthma with insulin resistance but not body weight in humans. In mice, co-development of obesity and HDM-induced lung inflammation attenuated inflammation in lung and perigonadal fat, with little impact on body weight, but small shifts in the composition of gut microbiota. Exposure to HDM improved glucose tolerance, reduced hepatosteatosis and increased energy expenditure and basal metabolic rate. These effects associate with increased activity of thermogenic adipose tissues independent of uncoupling protein 1.
CONCLUSIONS: Asthma associates with insulin resistance in humans, but HDM challenge results in opposing effects on glucose homeostasis in mice due to increased energy expenditure, reduced adipose inflammation and hepatosteatosis.
背景：在大多数国家，肥胖及其相关疾病和过敏的发病率正以惊人的速度上升。屋尘螨(HDM)具有高度过敏性，且暴露通常与城市久坐不动的室内生活方式有关，也会导致肥胖。
目的：本研究的目的是研究肺部炎症对肥胖和血糖稳态的流行病学关联和生理影响。
方法：采用基于人群的KORA-FF4队列中2207名成年人的流行病学数据，检测哮喘和鼻炎与体重和胰岛素敏感性指标之间的相关性。为了获得对功能的了解，采用HDM 对C57BL/6J小鼠进行鼻腔内致敏和激发，同时采用低脂或高脂饲料喂养12周，随后对肺、肝和脂肪组织进行详细的代谢和生化表型分析。
结果：我们发现人类哮喘与胰岛素抵抗直接相关，而与体重无关。在小鼠中，肥胖和HDM诱导的肺部炎症共同发展缓解了肺部和脂肪组织的炎症，对体重几乎没有影响，但肠道微生物群的组成发生了微小的变化。暴露于HDM可改善糖耐量，减少了肝脂肪变性，增加能量消耗和基础代谢率。这些效应与独立于解偶联蛋白 1 的产热脂肪组织活性增加有关。
结论：哮喘与人类胰岛素抵抗有关，但由于能量消耗增加，脂肪炎症和肝脂肪变性减少，在小鼠中HDM激发导致葡萄糖稳态的相反作用。
(中日友好医院呼吸与危重症医学科 王静茹 摘译 林江涛 审校)
(Allergy. 2022 Jan 20.doi: 10.1111/all.)
(Allergy. 2022 Jan 20.doi: 10.1111/all.)
Differential effects of lung inflammation on insulin resistance in humans and mice
Ruth Karlina, Claudia Flexeder, Stephanie Musiol, Madhumita Bhattacharyya, Evelyn Schneider, Irem Altun, Silvia Gschwendtner, Avidan U Neumann, Jana Nano, Michael Schloter, Annette Peters, Holger Schulz, Carsten B Schmidt-Weber, Marie Standl, Claudia Traidl-Hoffmann, Francesca Alessandrini, Siegfried Ussar
Abstract
BACKGROUND: The rates of obesity, its associated diseases, and allergies are raising at alarming rates in most countries. House dust mites (HDM) are highly allergenic and exposure often associates with an urban sedentary indoor lifestyle, also resulting in obesity.
OBJECTIVE：The aim of this study was to investigate the epidemiological association and physiological impact of lung inflammation on obesity and glucose homeostasis.
METHODS: Epidemiological data from 2,207 adults of the population-based KORA-FF4 cohort were used to test associations between asthma and rhinitis with metrics of body weight and insulin sensitivity. To obtain functional insights, C57BL/6J mice were intranasally sensitized and challenged with HDM and simultaneously fed with either low fat or high fat diet for 12 weeks followed by a detailed metabolic and biochemical phenotyping of the lung, liver and adipose tissues.
RESULTS: We found a direct association of asthma with insulin resistance but not body weight in humans. In mice, co-development of obesity and HDM-induced lung inflammation attenuated inflammation in lung and perigonadal fat, with little impact on body weight, but small shifts in the composition of gut microbiota. Exposure to HDM improved glucose tolerance, reduced hepatosteatosis and increased energy expenditure and basal metabolic rate. These effects associate with increased activity of thermogenic adipose tissues independent of uncoupling protein 1.
CONCLUSIONS: Asthma associates with insulin resistance in humans, but HDM challenge results in opposing effects on glucose homeostasis in mice due to increased energy expenditure, reduced adipose inflammation and hepatosteatosis.
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