Williams Kayla R, Bright Hoyt Atk, Fryer Allison D, Jacoby David B, Nie Zhenying
JCI Insight. 2025 Jan 9;10(1):e181070. doi: 10.1172/jci.insight.181070.
The impact of diet-induced maternal obesity on offspring airway hyperresponsiveness was studied in a diversity outbred mouse model that mirrors human genetic diversity. Female mice were started on high-fat or regular diet 8 weeks before breeding and throughout pregnancy and lactation. After weaning, all offspring were fed a regular diet. By 12 weeks, body weight and fat were increased in offspring of high-fat diet-fed dams, which was accompanied by metabolic dysfunction and hyperinsulinemia. This was followed by increased epithelial sensory innervation and increased bronchoconstriction to inhaled 5-hydroxytryptamine at 16 weeks. Bronchoconstriction was nerve mediated and blocked by vagotomy or atropine. A high-fat diet before pregnancy exerted the most influence on offspring airway physiology. Maternal obesity induced metabolic dysfunction and hyperinsulinemia, resulting in hyperinnervation and subsequent increased reflex-mediated hyperresponsiveness in their offspring. This is relevant to our understanding of asthma inheritance, considering the genetic diversity of humans.
在一个反映人类遗传多样性的多样化远交小鼠模型中，研究了饮食诱导的母体肥胖对后代气道高反应性的影响。雌性小鼠在繁殖前8周开始高脂饮食或常规饮食，并持续整个孕期和哺乳期。断奶后，所有后代均给予常规饮食。到12周时，高脂饮食喂养的母鼠后代的体重和脂肪增加，同时伴有代谢功能障碍和高胰岛素血症。随后，在16周时，上皮感觉神经支配增加，对吸入的5-羟色胺的支气管收缩增强。支气管收缩是由神经介导的，可被迷走神经切断术或阿托品阻断。怀孕前的高脂饮食对后代气道生理影响最大。母体肥胖导致代谢功能障碍和高胰岛素血症，导致神经支配过度，进而使其后代反射介导的高反应性增加。考虑到人类的遗传多样性，这与我们对哮喘遗传的理解相关。
