Maternal high-fat diet programs offspring airway hyperinnervation and hyperresponsiveness
Kayla R. Williams, Hoyt A.T.K. Bright, Allison D. Fryer, David B. Jacoby, Zhenying Nie
Kayla R. Williams, Hoyt A.T.K. Bright, Allison D. Fryer, David B. Jacoby, Zhenying Nie
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Research Article Metabolism Pulmonology

Maternal high-fat diet programs offspring airway hyperinnervation and hyperresponsiveness

Abstract

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.

Authors

Kayla R. Williams, Hoyt A.T.K. Bright, Allison D. Fryer, David B. Jacoby, Zhenying Nie

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Figure 9

Measuring airway hyperresponsiveness in offspring of dams given an HFD only during specific times critical for offspring development.

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Measuring airway hyperresponsiveness in offspring of dams given an HFD o...
(A). Female mice were fed an HFD before breeding only, during lactation only, or throughout pre-pregnancy, pregnancy, and lactation. Female mice fed an HFD or RD from 8 weeks before breeding until the end of lactation served as the controls. Offspring of mice fed an HFD before breeding only have similar increased airway response to 5-HT to offspring of mice fed HFD before, during, and after pregnancy (the latter data are reproduced from Figure 5 for ease of comparison). Bronchoconstriction in response to inhaled 5-HT in 16-week-old offspring born from dams on an HFD only during lactation was similar to that in offspring born from dams on an RD (B). Airway epithelial sensory nerve density was increased in offspring of dams fed an HFD before pregnancy, as well as those fed an HFD throughout pre-pregnancy, pregnancy, and lactation, but not in those fed an HFD during lactation only (C and D). In offspring of dams fed an HFD during all periods, body fat (E) was increased, lean mass (F) was decreased, and body weight (G) was increased. None of these changed in offspring of dams fed an HFD only pre-pregnancy or during lactation. Offspring physiology data were analyzed using a repeated 2-way ANOVA. Each data point represents the mean ± SEM, with n = 5–14; *P < 0.05. For offspring metabolic parameters, each symbol represents 1 animal, with n = 5–28. Data were analyzed using a 1-way ANOVA and presented as means ± SEM.