Exercise rescues obese mothers' insulin sensitivity, placental hypoxia and male offspring insulin sensitivity
Fernandez Twinn, DS
Nature Publishing Group
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Fernandez Twinn, D., Gascoin, G., Musial, B., Carr, S., Duque-Guimaraes, D., Blackmore, H., Alfaradhi, M., et al. (2017). Exercise rescues obese mothers' insulin sensitivity, placental hypoxia and male offspring insulin sensitivity. Scientific Reports, 7 (44650)https://doi.org/10.1038/srep44650
The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance. Maternal hyperinsulinemia (independent of maternal body weight and composition) strongly associated with offspring insulin resistance. To test causality, we implemented an exercise intervention that improved maternal insulin sensitivity without changing maternal body weight or composition. This maternal intervention prevented excess placental lipid deposition and hypoxia (independent of sex) and insulin resistance in male offspring. We conclude that hyperinsulinemia is a key programming factor and therefore an important interventional target during obese pregnancy, and propose moderate exercise as a promising strategy to improve metabolic outcome in both the obese mother and her offspring.
This work received funding from the European Union’s Seventh Framework Programme [FP7/2007-2013, project EarlyNutrition, grant agreement n°289346]; the MRC Metabolic Diseases Unit award [MC_UU_12012/4]; the Biotechnology and Biological Sciences Research Council [BB/M001636/1]; the British Heart Foundation (PG/14/20/30769) and the São Paulo Research Foundation (Process number: 2014/20380-5).
British Heart Foundation (PG/14/20/30769)
EC FP7 CP (289346)
British Heart Foundation (FS/09/029/27902)
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External DOI: https://doi.org/10.1038/srep44650
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263905
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