Prenatal alcohol exposure (PAE) affects at least 10% of newborns globally and leads to the development of fetal alcohol spectrum disorders (FASDs). Despite its high incidence, there is no consensus on the implications of PAE on metabolic disease risk in adults. Here, we describe a cohort of adults with FASDs that had an increased incidence of metabolic abnormalities, including type 2 diabetes, low HDL, high triglycerides, and female-specific overweight and obesity. Using a zebrafish model for PAE, we performed population studies to elucidate the metabolic disease seen in the clinical cohort. Embryonic alcohol exposure (EAE) in male zebrafish increased the propensity for diet-induced obesity and fasting hyperglycemia in adulthood. We identified several consequences of EAE that may contribute to these phenotypes, including a reduction in adult locomotor activity, alterations in visceral adipose tissue and hepatic development, and persistent diet-responsive transcriptional changes. Taken together, our findings define metabolic vulnerabilities due to EAE and provide evidence that behavioral changes and primary organ dysfunction contribute to resultant metabolic abnormalities.
Olivia Weeks, Gabriel D. Bossé, Isaac M. Oderberg, Sebastian Akle, Yariv Houvras, Paul J. Wrighton, Kyle LaBella, Isabelle Iversen, Sahar Tavakoli, Isaac Adatto, Arkadi Schwartz, Daan Kloosterman, Allison Tsomides, Michael E. Charness, Randall T. Peterson, Matthew L. Steinhauser, Pouneh K. Fazeli, Wolfram Goessling