Developmental programming of health and disease

Among the adult US population, cardiac and metabolic diseases have prevalences of 35% and 48%, respectively. It is traditionally believed that the risk of cardio-metabolic disease is determined by interactions among genetic and lifestyle factors. However, recently, it has become widely established that exposure to an adverse in utero environment also increases the risk of CVD in a phenomenon called developmental programming. The intrauterine environment is now considered one of the key determinants of cardiac and metabolic health in offspring. In the US, more than 65% of women who become pregnant are overweight or obese. Obesity in pregnancy programs the offspring to experience complications in adulthood, including obesity and cardiovascular and metabolic diseases.

We have utilized a mouse model of maternal high-fat diet-induced obesity that recapitulates metabolic perturbations seen in humans. We have shown that impaired immune function is crucial to this effect, with activation of chronic inflammation being required for the initiation and progression of developmental programming.  Our recent data reveal significant immunometabolic perturbations in the bone marrow of the newly weaned offspring born to obese mothers. Thus, adaptation to an adverse maternal intrauterine environment affects bone marrow metabolism at a very young age and might affect responses to immune challenges that appear later in life, for example, infections or cancer.

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