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.

Public Health Relevance

PROJECT #2: ROLE OF MATERNAL BARIATRIC SURGERY IN PROGRAMMING CARDIO- METABOLIC DISEASE IN GROWTH-RESTRICTED OFFSPRING NARRATIVE 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. This proposal will test the novel hypothesis that fetal exposure to elevated endogenous androgens in VSG dams in late pregnancy leads to a unique model of IUGR that programs impaired pancreatic beta cell function causing glucose intolerance and leptin resistance leading to obesity and hypertension in offspring. We further hypothesize that inappropriate activation of the renin angiotensin system contributes to increased blood pressure in IUGR offspring of VSG dams.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
1P20GM121334-01
Application #
9211438
Study Section
Special Emphasis Panel (ZGM1-RCB-9 (CI))
Project Start
2017-06-08
Project End
2022-05-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
1
Fiscal Year
2017
Total Cost
$270,885
Indirect Cost
$95,885
Name
University of Mississippi Medical Center
Department
Type
Domestic Higher Education
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
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