56 Revisiting the adipocyte number hypothesis and its implications for developmental programming

Abstract The strongest predictor of childhood obesity is being born to a mother who was obese during pregnancy, which is now the case for ∼30% of pregnancies in Canada and the USA. Therefore, women’s metabolic health during pregnancy is an important target for preventative measures aimed at addressing the obesity crisis. Our lab is exploring the role of adipose progenitors in programming early life adiposity and mediating the heightened risk for metabolic syndrome in offspring born to pregnancies complicated by obesity. The setpoint of adiposity is determined in early life by the number of adipocytes arising from a developmental pool of adipose progenitors that are specified to the adipocyte fate prior to birth. After puberty, adipocyte numbers remain stable throughout the rest of life. A pool of adipose progenitors residing in adult adipose depots serves as a reservoir to support adipocyte turnover, which is increased in obesity, and thereby plays a critical role in preserving metabolic health. Using a mouse model of diet-induced maternal obesity, our lab has shown that a perturbation in developmental adipogenesis, raises the setpoint of early life adiposity and predisposes to later-life adipose dysfunction and metabolic syndrome. Predisposition of offspring to metabolic dysfunction is sex-dependent, which our data demonstrate to be an estrogen-mediated sex difference arising at puberty rather than a programming effect. Together, our work provides new insight into the relationship between maternal obesity and childhood metabolic health and the modifying influence of sex. (Funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Natural Sciences and Engineering Research Council of Canada, and Diabetes Canada)