ZFIN ID: ZDB-PUB-200403-158
Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood
Weeks, O., Bossé, G.D., Oderberg, I.M., Akle, S., Houvras, Y., Wrighton, P.J., LaBella, K., Iversen, I., Tavakoli, S., Adatto, I., Schwartz, A., Kloosterman, D., Tsomides, A., Charness, M.E., Peterson, R.T., Steinhauser, M.L., Fazeli, P.K., Goessling, W.
Date: 2020
Source: The Journal of Clinical Investigation   130(5): 2252-2269 (Journal)
Registered Authors: Adatto, Isaac, Goessling, Wolfram, Houvras, Yariv, Peterson, Randall
Keywords: Development, Embryonic development, Metabolism, Obesity
MeSH Terms: none
PubMed: 32202514 Full text @ Journal of Clin. Invest.
ABSTRACT
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.
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