Abstract
Although prenatal alcohol exposure (PAE) reduces offspring growth, it may increase obesity risk at adolescence. Animal models of PAE display glucose intolerance and increased adiposity, suggesting that PAE causes metabolic reprogramming. We tested this hypothesis in a mouse model of binge PAE, wherein pregnant C57Bl/6J females received 3 g/kg alcohol (ETOH) daily from gestational day 12.5 to 17.5; maltodextrin (MD) and medium chain triglycerides (MCT) served as isocaloric nutritional controls, and sham (H2O) treatment controlled for gavage stress. Our comprehensive assessment quantified body composition, energy expenditure, glucose tolerance, and cardiovascular function in offspring at age 17 weeks. Although ETOH pups were initially lighter than all other groups, they did not have a unique obesogenic phenotype. Instead, a similar obesogenic phenotype emerged in all three caloric groups (MCT, MD, ETOH), such that caloric groups had greater post-weaning weight gain (both sexes), reduced gonadal fat weight (males), and reduced glucose clearance (males) compared against H2O offspring. PAE did not affect body composition, respiratory exchange ratio, metabolic adaption to high-fat or low-fat diet, eating behavior, and blood pressure, and ETOH values did not differ from those obtained from isocaloric controls. Exposure to a higher alcohol dose (4.5 g/kg) or a high-fat (60%) diet did not exacerbate differences in body composition or glucose tolerance. “PAE-specific” effects on postnatal growth, glucose tolerance, adiposity, or hypertension only emerged when PAE offspring were compared just against H2O controls, or against MD controls. We conclude that prior reports of obesity and glucose intolerance in adult PAE offspring reflect the contribution of added gestational calories, and not alcohol’s pharmacologic action. Results suggest that the increased adiposity risk in FASD is not caused by metabolic reprogramming, and instead originates from behavioral, medication, and/or dietary practices. This study highlights the importance of appropriate dietary controls in nutritional studies of PAE.
Highlights
Prenatal alcohol exposure (PAE) is a leading cause of neurodevelopmental disability and affects 2.5% - 4.5% of children [1]
Prenatal alcohol exposure and metabolic syndrome risk indirect calorimetry, whole body imaging, and glucose tolerance testing to comprehensively interrogate how PAE affects offspring metabolism, obesity risk, and feeding behavior. We address this in a mouse model of FASD that targets alcohol exposure to the post-morphogenetic period of fetal growth that was previously shown to be vulnerable to metabolic reprogramming [27, 30, 37]
Water [17,18,19,20] and carbohydrate [16, 21,22,23,24] were chosen for comparative purposes against studies employing those controls, and medium chain triglycerides (MCT) was chosen as a closer metabolic equivalent to alcohol, due to its rapid and direct metabolism that is independent of lipoprotein
Summary
Prenatal alcohol exposure (PAE) is a leading cause of neurodevelopmental disability and affects 2.5% - 4.5% of children [1]. PAE may increase chronic disease risk in later life [2]. PAE is associated with small-for-gestational age (SGA) [3,4,5,6], and because SGA itself significantly increases risk for childhood obesity [7], this has prompted suggestions that PAE may be an independent risk factor for obesity and metabolic syndrome in later life. Several studies document reduced fat mass in children who experienced PAE [4, 8], while others report an elevated incidence of overweight and obesity at adolescence and especially in females [12,13,14,15]. Data are lacking for adults with FASD, increased adiposity elevates risk for cardiovascular disease, type-two diabetes, and other obesity-associated chronic health problems which may signify an underlying metabolic disorder
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
