Determining the effect of in utero CBD exposure on eating behaviors, obesity, and insulin resistance

Susceptibility to obesity and Type 2 diabetes can be influenced by the intrauterine environment. Understanding how fetal exposures to substances that impact behavior and metabolism that may contribute to future metabolic disease risk is paramount to combating diabetes. Many women consume marijuana or its non-psychoactive component, cannabidiol (CBD) during pregnancy because it is readily available, can help with nausea, and public perception is that it is safe. However, the long-term effects on the offspring are not known. In adults, CBD may affect metabolic function, energy balance behaviors, and susceptibility to diabetes because it activates peroxisome proliferator-activated receptor (PPAR), which promotes of increased food intake and adiposity. Fetal exposure to another PPAR agonist rosiglitazone reduces expression of multiple components of insulin signaling, glucose transport, and energy sensing/lipid metabolism pathways. While PPAR is expressed in many metabolic tissues, we do not know if CBD exposure in utero is sufficient to induce changes in fetal or postnatal metabolism, behaviors that affect energy balance, or susceptibility to insulin resistance. Maternally consumed CBD diffuses across the placenta to the fetus. Retrospective clinical studies suggest fetal marijuana exposure is associated with lower birth weight and may impact fetal metabolism. However, these studies are limited by inadequate dosing information, inability to distinguish the impact of CBD from the psychoactive marijuana component, tetrahydrocannabinol (THC), and potential concurrent use of nicotine or alcohol. We will perform dose controlled animal studies to reveal whether and how fetal exposure to CBD affects eating behavior, body composition, and susceptibility to insulin resistance.