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.
Highlights
Alcohol and its primary metabolite, acetaldehyde, are teratogens, and exposure during gestation detrimentally affects fetal development [1,2,3]
To test the hypothesis that prenatal alcohol exposure (PAE) predisposes to cardiometabolic disease, we performed a retrospective cross-sectional study examining the incidence of metrics of cardiometabolic health in adults with any fetal alcohol spectrum disorders (FASDs) diagnosis, including fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD)
Using the patient database registry at a large academic health system (Research Patient Data registry [RPDR] of Partners HealthCare System), we identified male and female patients 18 years or older with FASDs (n = 208) and controls matched for age, sex, and race/ ethnicity (n = 208)
Summary
Alcohol and its primary metabolite, acetaldehyde, are teratogens, and exposure during gestation detrimentally affects fetal development [1,2,3]. More than 10% of pregnant women worldwide consume alcohol, and recent estimates suggest that 1% to 5% of US school-age children have fetal alcohol spectrum disorders (FASDs) [4,5,6,7]. FASD is an umbrella term describing a group of clinical conditions resulting from prenatal alcohol exposure (PAE), including fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD) [8]. FASD patients have variable features, including facial dysmorphology, microcephaly, cognitive and behavioral deficits, and organ malformations [7, 9,10,11]. The physiological effects of PAE are thought to last a lifetime; the metabolic health outcomes of FASDs on patients are not well understood [12].
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