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

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.