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Role of maternal bariatric surgery in programming cardio-metabolic disease in growth-restricted offspring

母亲减肥手术在生长受限后代心脏代谢疾病中的作用

基本信息

批准号：
9211438
负责人：
Bernadette E Grayson
金额：
$ 27.09万
依托单位：
UNIVERSITY OF MISSISSIPPI MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-08 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9211438
关键词：
Adverse effects Age Androgens Angiotensins Basic Science Birth Blood Pressure Body Weight decreased Cardiovascular Diseases Cell physiology Characteristics Child Child health care Clinical Comorbidity Data Development Doctor of Philosophy Duodenum Effectiveness Endocrinologist Esophagus Exhibits Exposure to Female Fertility Fetal Growth Retardation Gastrectomy Gastric Bypass Gestational Age Gestational Diabetes Glucose Intolerance Growth High Fat Diet High birth weight infant Hypertension Impairment Kidney Kidney Diseases Leptin resistance Life Link Mediating Mentors Mentorship Metabolic Metabolic Diseases Mississippi Modeling Molecular Obesity Operative Surgical Procedures Outcome Perinatal Physiological Plasma Play Pre-Eclampsia Pregnancy Premature Birth Procedures Rattus Renin-Angiotensin System Reporting Research Resolution Risk Risk Factors Rodent Rodent Model Role Serum Small for Gestational Age Infant Stomach Structure of beta Cell of islet Suggestion Techniques Testing Testosterone Tube Woman bariatric surgery cardiometabolic risk cardiovascular health child bearing early onset experimental study high risk human data male mortality neonatal death novel offspring postnatal prenatal exposure programs

项目摘要

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.

项目二格雷森