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.
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.
|Himel, Alexandra R; Cabral, Sharon A; Shaffery, James P et al. (2018) Anxiety behavior and hypothalamic-pituitary-adrenal axis altered in a female rat model of vertical sleeve gastrectomy. PLoS One 13:e0200026|
|Reckelhoff, Jane F (2018) Gender differences in hypertension. Curr Opin Nephrol Hypertens 27:176-181|
|Torres Fernandez, Edgar D; Adams, Kristen V; Syed, Maryam et al. (2018) Long-Lasting Androgen-Induced Cardiometabolic Effects in Polycystic Ovary Syndrome. J Endocr Soc 2:949-964|
|Reckelhoff, Jane F; Alexander, Barbara T (2018) Reproducibility in animal models of hypertension: a difficult problem. Biol Sex Differ 9:53|
|Spann, Redin A; Lawson, William J; Bidwell 3rd, Gene L et al. (2018) Rodent vertical sleeve gastrectomy alters maternal immune health and fetoplacental development. Clin Sci (Lond) 132:295-312|
|Mahajan, Gouri J; Vallender, Eric J; Garrett, Michael R et al. (2018) Altered neuro-inflammatory gene expression in hippocampus in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 82:177-186|
|Cunningham Jr, Mark W; Castillo, Javier; Ibrahim, Tarek et al. (2018) AT1-AA (Angiotensin II Type 1 Receptor Agonistic Autoantibody) Blockade Prevents Preeclamptic Symptoms in Placental Ischemic Rats. Hypertension 71:886-893|
|Patil, Chetan N; Racusen, Lorraine C; Reckelhoff, Jane F (2017) Consequences of advanced aging on renal function in chronic hyperandrogenemic female rat model: implications for aging women with polycystic ovary syndrome. Physiol Rep 5:|
|Yanes Cardozo, Licy L; Romero, Damian G; Reckelhoff, Jane F (2017) Cardiometabolic Features of Polycystic Ovary Syndrome: Role of Androgens. Physiology (Bethesda) 32:357-366|
|Ball, Jana P; Syed, Maryam; Marañon, Rodrigo O et al. (2017) Role and Regulation of MicroRNAs in Aldosterone-Mediated Cardiac Injury and Dysfunction in Male Rats. Endocrinology 158:1859-1874|
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