2011 — 2013 |
Grayson, Bernadette E |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Metabolic Consequences of Bariatric Surgery On Pregnant and Lactating Rats and Th @ University of Cincinnati
DESCRIPTION (provided by applicant): Presently 18.9% of women of childbearing age in the US are severely or morbidly obese with a BMI e 351. Besides having excess body weight, most also develop the "metabolic syndrome" which includes insulin resistance, impaired glucose tolerance and hypertension, triglycerides and cholesterol2. For women of childbearing age, obesity carries increased reproductive difficulties including decreased fertility, increased morbidity and mortality during pregnancy to both mother and offspring due to gestational diabetes, hypertension and preeclampsia, difficulties in delivery of large-for-gestational age (LGA) infants and decreased capacity and quality of breast milk in the postpartum period3-5. Furthermore, longitudinal human and animal studies indicate that the maternal in utero environment greatly affects the metabolic health of the offspring, with obese mothers more likely to have children with the metabolic syndrome6-9 While weight loss ameliorates many fertility and pregnancy problems as well as the comorbidities of the metabolic syndrome10, 11 ,long-term weight loss is difficult to achieve through food intake reduction and exercise, and the currently available pharmacologic treatments result in only small reductions in body weight. However, several bariatric surgeries produce sustained body weight reduction as well as amelioration of the comorbidities of metabolic syndrome, especially among severely or morbidly obese individuals. Although the benefits of these procedures to the recipient are obvious, a key question remains concerning the impact on pregnant mothers and their offspring. The goal of the proposed research is to determine the impact on reproductive cyclicity, pregnancy and lactation in female rats of two models of bariatric surgery: vertical sleeve gastrectomy (VSG), a restrictive procedure, and Roux-en-Y gastric bypass (RYGB), a restrictive/malabsorptive procedure. In particular, the hallmark side effects of each of these procedures will be evaluated in light of the important metabolic needs of pregnancy and lactation. Further, the postnatal effects of these procedures on the metabolic health of the offspring will be determined. PUBLIC HEALTH RELEVANCE: Presently 18.9% of women in the U.S. are considered either severely or morbidly obese. Increasing numbers of individuals are pursuing bariatric surgery of which 80% are women. Using rodent models of bariatric surgery, we aim to determine the reproductive and metabolic effects on mother and offspring.
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0.955 |
2017 — 2019 |
Grayson, Bernadette E |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Role of Maternal Bariatric Surgery in Programming Cardio-Metabolic Disease in Growth-Restricted Offspring @ University of Mississippi Med Ctr
Project 2 Grayson ABSTRACT Role of maternal bariatric surgery in programming cardiovascular disease in offspring Bariatric surgery for long term body weight loss and resolution of obesity-associated comorbidities has gained popularity in recent decades. Vertical sleeve gastrectomy (VSG) is a surgical weight loss procedure that resects 80% of the stomach creating a tube linking the esophagus to the duodenum.Because of the great effectiveness and relative simplicity of the VSG surgery, VSG is now on the rise in the U.S. >80% of the recipients of VSG are women of whom approximately half are of child-bearing age. VSG in female rodents has similar characteristics of women undergoing VSG. Women who have undergone bariatric surgery have a lower risk of gestational diabetes and preeclampsia, and reduced risk of large-for-gestational age (LGA) babies. However, recent reports also highlight negative outcomes in women with previous bariatric surgery that include an increased risk for small-for-gestational age babies (SGA) or IUGR birth at a reduced gestational age or preterm birth, and still birth or neonatal death. We were the first to show in our model of rodent VSG, that offspring had IUGR and increased mortality in the absence of identifiable negative outcomes in the dam. My novel preliminary data indicate that maternal plasma testosterone is increased in VSG dams during late pregnancy, and we hypothesize that this could play a role in the developmental programming of increased cardio-renal risk of the IUGR offspring. This proposal will test the novel hypothesis that prenatal exposure to increased endogenous levels of testosterone in VSG dams increases the risk for cardio-metabolic abnormalities in male and female IUGR offspring. (1) We will test the hypothesis that fetal exposure to elevated maternal endogenous levels of testosterone in VSG dams programs glucose intolerance mediated by impaired pancreatic beta cell function and leptin resistance leading to obesity and hypertension in IUGR offspring. (2) We will test the hypothesis that fetal exposure to elevated maternal endogenous levels of testosterone in VSG dams programs activation of the renin-angiotensin system leading to elevated blood pressure in IUGR offspring.
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0.985 |