Maternal high‐fat diet in mice leads to innate airway hyperresponsiveness in the adult offspring

Abstract

Maternal obesity prior to and during pregnancy has been associated with an increased incidence of childhood asthma. As diets rich in saturated fat are linked to obesity and inflammation, we created a murine model to investigate the effect of maternal high‐fat diet (HFD) on adult offspring airway hyperreactivity (AHR), a cardinal feature of asthma. Balb/cByJ dams were fed a HFD (60% fat Calories) or normal‐fat diet (NFD) (10% fat Calories) from 8 weeks prior to first breeding through their pregnancies. Pups were weaned to either a HFD or NFD (at 4 weeks of age). AHR was measured in the 10‐week‐old offspring following inhaled methacholine challenge by end‐inflation technique. Bronchial alveolar lavage fluid (BALF) was analyzed for cell count, total protein, and IL‐6. Offspring of HFD dams weaned to NFD had increased AHR compared to offspring of NFD dams weaned to NFD. Offspring of HFD dams that remained on HFDs had increased AHR compared to offspring of NFD dams weaned to HFDs. Offspring of HFD dams had higher BALF cell counts, higher neutrophil percentage, greater total protein, and IL‐6 in the BALF. These results demonstrate that a maternal diet high in saturated fat through pregnancy and lactation plays a key role in programming adult offspring AHR.

Maternal high-fat diet alters lung development and function in the offspring

“…However, we cannot rule out that the changes we observe in NFB-related proteins are not because of the influence of the increased number of macrophages rather than from lung tissues. Our data agree with that reported by Song et al (28) in rat pups exposed to maternal HFD with greater numbers of inflammatory cells within the lung tissues and with MacDonald et al (22) in Balb/cByJ mice exposed to maternal HFD with elevated lL-6 levels and increased numbers of neutrophils in the bronchoalveolar lavage fluid. Furthermore, Zabolotny et al (34) reported that increases in TNF␣ expression activates the NFB p65 subunit, which in turn, binds to the promoter of PTP1B and induces its expression both in vitro and in vivo.…”

“…6C). Again, this is different than the PFTs reported in rat pups exposed to maternal obesity and the studies in the Balb/cByj mice (3,22). In rats, PFT increases in pressure volume loop area and decreases in compliance were observed in response to streptozotocin treatment, but no differences were observed because of diet alone.…”

Maternal Obesity in Mice Exacerbates the Allergic Inflammatory Response in the Airways of Male Offspring

“…We have found no differences in leukocytes in BAL when comparing SC/SHAM to HFD/SHAM mice. This is in apparent contrast to the study published by MacDonald et al [18]. Those researchers found increased leukocytes in BAL of mice born to HFD-fed mice.…”

“…Human studies have shown that maternal obesity during pregnancy and increased gestational weight gain were positively associated with the risk of childhood asthma [16,17]. In accordance with those findings, it was also described that non-allergen-sensitized mice and rats born to mothers exposed to HFD during pregnancy and lactation spontaneously develop lower respiratory system compliance and higher respiratory system resistance [18,19]. Similar data were found in adult non-allergen-sensitized offspring of mice breastfed by dams consuming HFD [20].…”

“…MacDonald et al have demonstrated that the male and female offspring of BALB/cByJ mice born to and breastfed by mothers receiving HFD manifest increased methacholine-induced respiratory resistance and increased neutrophil count and IL-6 level in BAL samples [18]. Dinger et al, instead, used C57B6 mice to show that feeding dams with HFD during lactation caused greater airway resistance in the male offspring not exposed to OVA [20].…”