PUBLICATION
Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood
- Authors
- 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.
- ID
- ZDB-PUB-200403-158
- 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
- Datasets
- GEO:GSE142311
- MeSH Terms
-
- Adult
- Animals
- Diabetes Mellitus, Type 2*/etiology
- Diabetes Mellitus, Type 2*/metabolism
- Diabetes Mellitus, Type 2*/pathology
- Female
- Fetal Alcohol Spectrum Disorders*/metabolism
- Fetal Alcohol Spectrum Disorders*/pathology
- Humans
- Infant, Newborn
- Intra-Abdominal Fat/metabolism
- Intra-Abdominal Fat/pathology
- Liver/metabolism
- Liver/pathology
- Male
- Mice
- Mice, Transgenic
- Obesity*/etiology
- Obesity*/metabolism
- Obesity*/pathology
- Pregnancy
- Prenatal Exposure Delayed Effects*/metabolism
- Prenatal Exposure Delayed Effects*/pathology
- Registries
- Zebrafish
- PubMed
- 32202514 Full text @ Journal of Clin. Invest.
Citation
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. (2020) Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood. The Journal of Clinical Investigation. 130(5):2252-2269.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping