Childhood obesity rates are at their highest recorded level of 17%, and an important emerging risk factor is maternal obesity. It is hypothesized that maternal obesity during critical stages of in utero development programs the risk for the development of obesity in the offspring, but the mechanism for this transmission remains unclear. One of the most efficient and long-lasting therapies for obesity in reproductive-age women is Roux-en-Y gastric bypass (RYGB) surgery, and recent results suggest that maternal RYGB may protect offspring from the development of obesity. However, conflicting data also indicates maternal RYGB may result in fetal malnutrition, which could have a lasting detrimental impact on offspring health. In the current proposal, we will utilize our long-standing nonhuman primate model of maternal western-style diet (WSD) consumption in conjunction with our newly developed model of nonhuman primate RYGB to determine how RYGB impacts both maternal health and offspring development. Previous work from our laboratory has found that fetal nonhuman primates exposed to a WSD in utero have a number of physiological changes, including alterations in postnatal growth curves and insulin sensitivity along with alterations in the pancreas. These findings will be the foundation to explore what, if any, beneficial impact maternal RYGB has to reverse these in utero WSD- induced alterations in offspring physiology. One novel mechanism by which maternal RYGB may impact offspring metabolic health is the microbiome. Our previous work has demonstrated that maternal diet and microbiome composition may have a long-term influence on the offspring microbiome. RYGB causes drastic changes to the patient's microbiome, which appear to promote weight-loss when transferred into germ-free mice. To our knowledge, no previous study has investigated how maternal RYGB may impact offspring microbiome and whether this alters metabolic physiology. The current research proposal hopes to address how RYGB impact both maternal metabolic health during pregnancy as well as offspring fetal growth and postnatal metabolic health with three specific aims:
Specific Aim 1. Characterize the effect of RYGB on maternal metabolic health during pregnancy.
Specific Aim 2. Determine the impact of maternal RYGB on offspring fetal growth and early postnatal metabolic health.
Specific Aim 3. Assess the impact of RYGB on maternal and offspring microbiome.
Roux-en-Y gastric bypass (RYGB) is an increasingly prevalent surgical intervention for the treatment of obesity, but the impact of this surgery on female patients' future pregnancy health and offspring development is unclear. While some clinical studies have shown maternal RYGB improves offspring outcomes associated with maternal obesity, others have demonstrated detrimental effects such as fetal malnutrition. The current proposal will investigate how maternal RYGB affects the development of offspring in a nonhuman primate model and explore the microbiome as a possible mechanism by which metabolic changes associated with RYGB may be passed from mother to offspring.
