ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This review combined findings from human and rodent studies on the maternal factors that influence the neurodevelopmental programming of long-term adiposity. It highlights the roles of maternal nutritional status, metabolic hormones and epigenetic changes during gestation and the postnatal period on the programming of body weight in the offspring, and their impact on the development of hypothalamic, brain stem, and hedonic circuits within the central nervous system.

This review raises some critical considerations for obesity and obesity-related disease prevention. Maternal obesity or overnutrition during the prenatal and postnatal periods are major determinants in programming body weight in the offspring. Effects of maternal obesity can accumulate through epigenetic marks over successive generations to shift the population distribution toward increased adult body weight (1). Optimization of maternal body mass/composition and nutrition during the third trimester and neonatal nutrition are important goals to decrease the lifetime obesity risk in offspring.

In utero and early postnatal insulin and leptin exposure is another important contributor in adiposity programming. Exposure to elevated levels of insulin is associated with increased body weight gain, glucose impairment and altered hypothalamic circuits in the offspring (2, 3). Both reduced and augmented leptin surges during the immediate postnatal period are associated with increased adult body weight (4). Fetal hyperinsulinemia due to maternal hyperglycemia is associated with increased fat accrual and higher fetal circulating leptin concentration. It can be concluded that an optimal concentration of these hormones is desirable during early life.

Current interventions in obese women have only a mild or no effect on offspring outcomes regarding birth weight and fat accumulation (5, 6). Understanding the complex neuro-molecular pathways for the developmental programming of adiposity may help to design preventive strategies as well as therapeutic approaches to prevent the transgenerational transmission of obesity. Reducing body weight and improving metabolic health in women prior to conception could have the most profound impact, not only on maternal and offspring outcomes, but also on the health of future generations.

References: 1. Waterland RA, Travisano M, Tahiliani KG, Rached MT, Mirza S. Methyl donor supplementation prevents transgenerational amplification of obesity. Int J Obes (Lond). 2008;32(9):1373-9.2. Plagemann A, Heidrich I, Götz F, Rohde W, Dörner G. Lifelong enhanced diabetes susceptibility and obesity after temporary intrahypothalamic hyperinsulinism during brain organization. Exp Clin Endocrinol. 1992;99(2):91-5.3. Carmody JS, Wan P, Accili D, Zeltser LM, Leibel RL. Respective contributions of maternal insulin resistance and diet to metabolic and hypothalamic phenotypes of progeny. Obesity (Silver Spring). 2011;19(3):492-9.4. Attig L, Solomon G, Ferezou J, Abdennebi-Najar L, Taouis M, Gertler A, et al. Early postnatal leptin blockage leads to a long-term leptin resistance and susceptibility to diet-induced obesity in rats. Int J Obes (Lond). 2008;32(7):1153-60.5. Dodd JM, Turnbull D, McPhee AJ, Deussen AR, Grivell RM, Yelland LN, et al. Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial. Bmj. 2014;348:g1285.6. Grivell RM, Yelland LN, Deussen A, Crowther CA, Dodd JM. Antenatal dietary and lifestyle advice for women who are overweight or obese and the effect on fetal growth and adiposity: the LIMIT randomised trial. Bjog. 2016;123(2):233-43.