Mechanisms Underlying the Association between Maternal and Offspring Obesity

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DESCRIPTION (provided by applicant): I am a 4th year postdoctoral fellow preparing to transition to a junior faculty position. During my postdoctoral training, I have been actively engaged in research regarding prenatal programming of childhood obesity risk. I bring to this research a diverse training background in psychology, behavioral neuroscience, nutrition, and metabolism, as indicated by my publishing record. At this juncture, I seek an NIDDK-sponsored K01 award to support a project that will investigate mechanisms underlying prenatal programming, while concurrently providing me with the opportunity to obtain further training in physiological and behavioral predictors of childhood obesity. In addition, I will use this protected time to train in the design and conduct of clinical trials, particularly pertaining to behavioral interventions with longitudinal outcomes. These activities will ultimately help me to build a career in translating findings from basic research into feasible behavioral interventions to reduce the risk of obesity among offspring of obese women. The institution within which I will undertake my Career Development Plan is the University of Alabama at Birmingham (UAB). This highly successful institution maintains a supportive environment for training junior investigators, with many resources that facilitate both research and training. I have selected a team of two mentors with complementary expertise, one of whom is external to UAB but is a leader in the field of maternal obesity and prenatal programming. They have helped me to select three consultants who will oversee the implementation of research protocols, and a three-member career advisory panel that will monitor the progress of my career and the achievement of my short- and long-term goals. The revised project and training plan described in this application reflect the input of each member of this team. The proposed project will examine independent effects of maternal obesity and metabolic health on offspring risk for obesity. At least a portion of the risk for offspring obesity is believed to be attributable to excess fuel delivery to the developing fetus, which alters programming of fetal metabolism that ultimately may contribute to excess deposition of adipose tissue. Consequently, offspring of obese women are at greater risk because obesity-related metabolic abnormalities, such as reduced insulin sensitivity and abnormal substrate metabolism, increase the availability of fuel to the fetus. It is not known, however, whether maternal obesity in the absence of poor metabolic health will contribute to offspring risk for obesity. Similarly, normal weight women may be dichotomized into those of good or poor metabolic health. The overall goal of this study is to test the hypothesis that offspring of obese but metabolically healthy women have less risk for obesity as compared to offspring of metabolically unhealthy women. Using a two-way factorial design, women will be recruited to fill normal weight vs. obese, high vs. low fasting glucose groups. Glucose and lipid metabolism will be rigorously assessed to examine whether fasting glucose is a useful screening tool for poor metabolic health during pregnancy (Specific Aim 1). The independent effects of maternal obesity and metabolic health on neonatal adiposity and umbilical cord C-peptide will be assessed (Specific Aim 2). Finally, a hypothesized pathway linking maternal weight and substrate metabolism, to fetal insulin, and to subsequent weight gain at 0- 3 years will be tested (Specific Aim 3). The novelty of the proposed study lies in the examination of the independent effects of maternal obesity and metabolic health on mechanisms underlying the prenatal programming of childhood obesity risk. If, as hypothesized, maternal metabolic health has a greater influence on offspring risk than does maternal obesity, future intervention efforts can focus on maintaining optimal metabolic health during pregnancy, irrespective of weight status.