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Programming of adiposity in female offspring by maternal obesity and exercise Melanson, James

Abstract

INTRODUCTION: In Canada, nearly half of women of child-bearing age are overweight (BMI 25-29.9 kg/m²) or obese (BMI ≥30 kg/m²). Current guidelines recommend moderate exercise for all pregnant women. However, little is known about the effect of exercise during pregnancy on the developing offspring. Rodent studies demonstrate that offspring from dams fed a high-fat diet have vessel-specific impairment in endothelium-dependent vascular function, greater adiposity, and impairments in glucose homeostasis. Further, offspring from exercised dams have improved glucose homeostasis. OBJECTIVE: In this thesis, I determined if maternal exercise during pregnancy mitigates the adverse effects of maternal obesity on offspring adiposity, glucose homeostasis, and vascular health in female offspring. METHODS: Dams (C57BL/6) were fed a control (10% energy from fat) or western diet (45% energy from fat) from weaning for 13 weeks and through breeding, pregnancy, and lactation. Just prior to breeding, dams were put into cages with or without a running wheel for voluntary exercise through breeding, pregnancy, and lactation. Offspring were weaned onto the control or western diet and maintained on the diet for 20 weeks; only female offspring were studied. Lean and fat mass were quantified by ¹H-NMR. Intraperitoneal insulin tolerance (IPITT), glucose tolerance (IPGTT) and insulin secretion tests (IPIST) were performed prior to the end of the feeding period. Vascular endothelial-dependent and independent dilatation were assessed ex vivo by isometric force measurements of aortic rings in response to phenylephrine, acetylcholine, and sodium nitroprusside. RESULTS: Weaning weights were greater in offspring from western-fed dams than control-fed dams. Control-fed offspring from western-fed dams had higher heart and kidney weights than those from control-fed dams. Control-fed offspring from exercised dams had higher blood glucose concentrations at IPGTT₃₀minutes than those from sedentary dams. Western-fed offspring from exercised dams had greater body weights, retroperitoneal fat weights, and Il10 mRNA in retroperitoneal adipose tissue, and lower blood glucose concentrations at IPGTT₉₀minutes than those from sedentary dams. Endothelium-dependent vasorelaxation of thoracic aortae was likely unaffected by maternal western diet or maternal exercise in control-fed and western-fed offspring. CONCLUSION: These findings suggest maternal exercise is beneficial in improving glucose homeostasis and adiposity in western-fed female offspring.

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