SAT-LB104 Maternal Non-Nutritive Sweeteners Consumption Perturbs Development of Melanocortin Circuits Causing Long-Term Metabolic Alterations in the Offspring

Maternal Non-Nutritive Sweeteners Consumption Perturbs Development of Melanocortin Circuits Causing Long-Term Metabolic Alterations in the Offspring Soyoung Park(1), Alice Jang(1), Josephine Lowy(1), Sebastien G Bouret(2 1)Developmental Neuroscience & Diabetes and Obesity Programs, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, USA. (2) Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, UMR-S 1172, Lille, 59000, France. With the growing prevalence of obesity and diabetes, including among pregnant women, non-nutritive sweeteners (NNS) have been widely used as an alternative to sugar in the attempt to deliver a sweet taste without excessive caloric load. However, there is little evidence regarding their biological effects particularly during critical periods of growth and development. In this study, we aimed to investigate whether maternal NNS consumption causes long-term neurodevelopmental and metabolic perturbations in the offspring. Adult female wild-type mice were exposed to either water (control), aspartame (0.03%), or rebaudioside A (0.02%) throughout pregnancy and lactation. Adult male, but not female, offspring from both aspartame- and rebaudioside A-exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal NNS consumption impaired pro-opiomelanocortin axonal projections to the paraventricular nucleus of the hypothalamus as well as reduced parasympathetic innervation of pancreatic islets. Taken together, our data indicate that maternal NNS consumption causes neurodevelopmental abnormalities in the offspring that may contribute to lifelong metabolic dysregulations.