Citation:

Gavett, S., M. Hargrove, S. Snow, P. Phillips, C. Gordon, AND U. Kodavanti. Timing of Rat Gestational High-Fat Diet and Sex Determine Increased Susceptibility to Allergic Responses in Offspring. Society of Toxicology, Baltimore, MD, March 10 - 14, 2019.

Impact/Purpose:

A maternal lifestyle of consumption of a diet high in fats and calorically rich components could have negative consequences on offspring in terms of susceptibility to air pollutants. This study examined the effects of a high-fat diet (HFD) given throughout pregnancy or in the first or second halves of pregnancy on allergic responses in male and female rat offspring. Female offspring of dams given HFD were hyperresponsive to methacholine challenge, while male offspring had increased indicator of lung injury. This study suggests maternal diet is a significant factor in determining susceptibility to air pollution.

Description:

We previously showed offspring from Long-Evans rat dams given a high-fat diet (HFD) before, during, and after pregnancy had increased pulmonary and metabolic responses to acute ozone exposure. Increased susceptibility to allergy and asthma may also result from maternal HFD consumption. To determine if there is a window of susceptibility to allergic responses in offspring due to HFD consumption during gestation, dams were fed a control diet (CD) throughout gestation, HFD on gestation days (GD) 1-11 followed by CD on GD 12-22 (HFD/CD), CD from GD 1-11 followed by HFD on GD 12-22 (CD/HFD), or HFD throughout gestation (HFD). Male and female offspring (average 16 weeks old on day 0) were sensitized intranasally (i.n.) with 10 g house dust mite (HDM) antigen on days 0 and 7 and challenged i.n. on day 21. Non-allergic rats received saline vehicle only on sensitization days. Respiratory responses to methacholine aerosol (0, 10, 20, and 40 mg/ml saline) were assessed by whole body plethysmography 2 days after challenge. Enhanced pause (PenH), an indicator of labored breathing, was significantly increased in female HDM-allergic HFD and CD/HFD groups compared with the female allergic CD group during 40 mg/ml MCh exposure. There were no differences among male groups, and other indices of respiratory function were not affected by maternal diet in non-allergic or HDM-allergic groups. Alveolar macrophages constituted ~99% of bronchoalveolar lavage fluid (BALF) cells in all non-allergic groups. BALF neutrophils, eosinophils, and lymphocytes together comprised ~6% (females) to ~12% (males) of total cells in HDM-allergic groups, indicating mild allergic inflammation, but there were no effects of maternal diet on inflammatory responses. Maternal diet also had no influence on BALF protein and albumin, which were increased in HDM-allergic groups compared with non-allergic groups. In contrast, BALF -glutamyl transferase, a marker of lung injury, was significantly increased (1.8-1.9-fold) in both non-allergic and HDM-allergic CD/HFD and HFD male groups compared with CD males. Together these data suggest increased susceptibility to allergic airway hyperresponsiveness in female offspring due to maternal HFD throughout or in the latter half of pregnancy. Greater lung injury in male offspring due to the same maternal diets may predispose to increased susceptibility to air pollutants. (This abstract does not reflect USEPA policy.)

Record Details: