Maternal high fat diet compromises survival and modulates lung development of offspring, and impairs lung function of dams (female mice)

Jordan Smoothy,Alexander N Larcombe,Shelley Gorman,Emily K Chivers,Vance B Matthews

doi:10.1186/s12931-019-0976-3

Abstract

BackgroundEpidemiological studies have identified strong relationships between maternal obesity and offspring respiratory dysfunction; however, the causal direction is not known. We tested whether maternal obesity alters respiratory function of offspring in early life.MethodsFemale C57Bl/6 J mice were fed a high or low fat diet prior to and during two rounds of mating and resulting pregnancies with offspring lung function assessed at 2 weeks of age. The lung function of dams was measured at 33 weeks of age.ResultsA high fat diet caused significant weight gain prior to conception with dams exhibiting elevated fasting glucose, and glucose intolerance. The number of surviving litters was significantly less for dams fed a high fat diet, and surviving offspring weighed more, were longer and had larger lung volumes than those born to dams fed a low fat diet. The larger lung volumes significantly correlated in a linear fashion with body length. Pups born from the second pregnancy had reduced tissue elastance compared to pups born from the first pregnancy, regardless of the dam’s diet. As there was reduced offspring survival born to dams fed a high fat diet, the statistical power of lung function measures of offspring was limited. There were signs of increased inflammation in the bronchoalveolar lavage fluid of dams (but not offspring) fed a high fat diet, with more tumour necrosis factor-α, interleukin(IL)-5, IL-33 and leptin detected. Dams that were fed a high fat diet and became pregnant twice had reduced fasting glucose immediately prior to the second mating, and lower levels of IL-33 and leptin in bronchoalveolar lavage fluid.ConclusionsWhile maternal high fat diet compromised litter survival, it also promoted somatic and lung growth (increased lung volume) in the offspring. Further studies are required to examine downstream effects of this enhanced lung volume on respiratory function in disease settings.

Highlights

Epidemiological studies have identified strong relationships between maternal obesity and offspring respiratory dysfunction; the causal direction is not known
In the week prior to first mating (Fig. 1), results of a Glucose tolerance test (GTT) indicated that dams fed the high fat diet had developed signs of glucose intolerance, with increased glucose levels observed throughout the GTT, with increased area under the curve of the GTT in mice fed a high fat diet compared with control mice (Fig. 3c, d)
Fewer litters born to dams fed a high fat diet survived until 2 weeks of age For either pregnancy, there was no difference in the number of mice with confirmed pregnancies, the time for pregnancies to be confirmed or weight gain during the first 10 days of pregnancy, for dams fed a high or low fat diet (Table 2)

Summary

Introduction

Epidemiological studies have identified strong relationships between maternal obesity and offspring respiratory dysfunction; the causal direction is not known. There is up to a 50% increased odds of asthma in children of obese/overweight mothers (reviewed in [3]). These observations suggest that maternal obesity could contribute significantly towards asthma susceptibility and other associated respiratory problems (like those induced by viral infection). While direct foetal programming could explain the observed positive relationships between maternal obesity and offspring asthma, it is quite plausible that they are confounded by either shared environmental or genetic risk factors for both maternal obesity and childhood asthma. Epidemiological studies do not prove that maternal obesity is a cause of childhood asthma, and may be confounded by environmental or genetic risk factors, for example, excessive gestational weight gain [5]

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