Fifty-percent of pregnant women in the US are overweight or obese, putting not only the mother’s health at risk but also placing a substantial health care burden on future generations before they are even born. Maternal pre-pregnancy obesity is associated with excessive gestational weight gain (GWG) and metabolic adverse in utero and postnatal environments that expose offspring to exaggerated developmental signals (e.g. hormones, glucose, lipids, and inflammatory mediators) that negatively impact disease risk outcomes in adulthood. The Institute of Medicine recommends that overweight/obese expectant mothers receive dietary and exercise counselling to limit GWG, however, most obese women demonstrate modest and variable responses to lifestyle interventions during pregnancy for various practical (lack of time, motivation) and physiological (change in appetite, fatigue) reasons. Although women may be motivated to improve eating patterns, a lack of improvement in dietary quality both before and during pregnancy has been reported. Further, although the pre-pregnancy period is regarded as a critical window where lifestyle changes could prevent harmful child outcomes, the high rate of unplanned pregnancies (51% in the US) do not provide this opportunity. Given the breadth of current limitations in lifestyle interventions to improve maternal pre-pregnancy BMI and limit GWG, there is a serious lack of treatment options that effectively address the ever-growing problem of maternal obesity. A promising, yet essentially unexplored, option may be found in dietary supplementation of natural health products with established anti-obesity and metabolic health-promoting responses. α-lipoic acid (αLPA) is notable amongst nutraceuticals as it offers a wide array of metabolic benefits with purported anti-obesity, appetite-suppressing, glucose lowering, and insulin sensitizing effects. However, it has yet to be examined in the context of maternal obesity as a preventative therapy to protect against adverse programming outcomes. Therefore, our proposal has two Specific Aims: i) To characterize maternal and fetal metabolic adaptations to dietary αLPA supplementation in obese pregnancies; and ii) To determine the influence of maternal αLPA supplementation in protecting against perinatal programming of obesity and associated metabolic dysfunction in offspring throughout the life course. We will use a well-characterized diet-induced obese pregnancy rat model to malprogram fetal pancreatic beta cell function and hypothalamic appetite-regulating neuropeptide signaling resulting in adult-onset obesity and glucose intolerance. The safety and efficacy of maternal αLPA supplementation throughout pre- pregnancy, gestation, and lactation will be explored as a means to protect against maladaptive programming responses in offspring from obese pregnancies. The ideas in this proposal should be considered highly exploratory that, if successful, would have a high degree of impact for early obesity prevention strategies and provide an informed understanding to advance novel applications for αLPA.

Obese pregnancies are associated with adverse in utero and postnatal nutritional environments that programs enhanced susceptibility to adult-onset obesity and metabolic disease risk in offspring. This proposal will explore dietary supplementation of α-lipoic acid as a means to protect against maladaptive programming of obesity in offspring.