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.
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.
|Ressler, Ilana B; Grayson, Bernadette E; Ulrich-Lai, Yvonne M et al. (2015) Diet-induced obesity exacerbates metabolic and behavioral effects of polycystic ovary syndrome in a rodent model. Am J Physiol Endocrinol Metab 308:E1076-84|
|Grayson, B E; Fitzgerald, M F; Hakala-Finch, A P et al. (2014) Improvements in hippocampal-dependent memory and microglial infiltration with calorie restriction and gastric bypass surgery, but not with vertical sleeve gastrectomy. Int J Obes (Lond) 38:349-56|
|Chambers, Adam P; Smith, Eric P; Begg, Denovan P et al. (2014) Regulation of gastric emptying rate and its role in nutrient-induced GLP-1 secretion in rats after vertical sleeve gastrectomy. Am J Physiol Endocrinol Metab 306:E424-32|
|Grayson, Bernadette E; Hakala-Finch, Andrew P; Kekulawala, Melani et al. (2014) Weight loss by calorie restriction versus bariatric surgery differentially regulates the hypothalamo-pituitary-adrenocortical axis in male rats. Stress 17:484-93|
|Ressler, Ilana B; Grayson, Bernadette E; Seeley, Randy J (2014) Metabolic, behavioral, and reproductive effects of vertical sleeve gastrectomy in an obese rat model of polycystic ovary syndrome. Obes Surg 24:866-76|
|Grayson, Bernadette E; Seeley, Randy J; Sandoval, Darleen A (2013) Wired on sugar: the role of the CNS in the regulation of glucose homeostasis. Nat Rev Neurosci 14:24-37|
|Grayson, Bernadette E; Schneider, Katarina M; Woods, Stephen C et al. (2013) Improved rodent maternal metabolism but reduced intrauterine growth after vertical sleeve gastrectomy. Sci Transl Med 5:199ra112|
|Grayson, B E; Seeley, R J (2012) Deconstructing obesity: the face of fatness before and after the discovery of leptin. Diabetologia 55:3-6|