Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood
Olivia Weeks, … , Pouneh K. Fazeli, Wolfram Goessling
Olivia Weeks, … , Pouneh K. Fazeli, Wolfram Goessling
Published March 23, 2020
Citation Information: J Clin Invest. 2020;130(5):2252-2269. https://doi.org/10.1172/JCI132139.
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Research Article Development Metabolism

Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood

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.

Authors

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

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Figure 3

EAE is a risk factor for increased visceral adiposity in adulthood.

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EAE is a risk factor for increased visceral adiposity in adulthood. (A) ...
(A) Nile red staining of internal organs and VAT visualized after skin and body wall muscle removal. Scale bars: 1 mm. (B) Quantification of VAT area before diet challenge. 1% EtOH–exposed (12 hpf–5 dpf) males have a larger VAT depot than controls at 65 dpf. *P = 0.0497, Student’s unpaired 2-tailed t test. (C) Quantification of VAT area after 4 weeks of diet challenge. EAE adults have a larger VAT than controls in response to HFHC. *P = 0.0103; ****P < 0.0001, 2-way ANOVA with Tukey’s multiple comparisons test. (D) Quantification of VAT area after 10 weeks of diet challenge. EAE adults receiving the ND have a larger VAT than controls. *P = 0.0102, Student’s 2-tailed unpaired t test. HFHC diet induces significant gains in VAT area in both control and EAE adults (*P = 0.0228 [1% EtOH ND versus HFHC], ****P < 0.0001 [0% EtOH ND versus HFHC], 2-way ANOVA Tukey’s multiple comparisons test). (E) H&E staining of PVAT following 4 weeks of diet challenge. Scale bars: 0.01 mm. (F) Quantification of PVAT adipocyte diameter following normal and HFHC diet. **P = 0.001, 2-way ANOVA. (G) Nile red staining of SAT (dotted white outline). Scale bars: 1 mm. Body-wide quantification of SAT was accomplished by combining 2 photos in ImageJ using collage photomerge. (H) Quantification of SAT area after 4 weeks of diet challenge. ****P < 0.0001, 2-way ANOVA Tukey’s multiple comparisons test. Error bars show mean with SD. Sample numbers (n) noted under figure panels.