Alcohol blunts pregnancy-mediated insulin resistance and reduces fetal brain glucose despite elevated fetal gluconeogenesis, and these changes associate with fetal weight outcomes
Corresponding Author
Nipun Saini
Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Correspondence
Nipun Saini, Nutrition Research Institute, Rm 3111, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC 28081, USA.
Email: [email protected]
Search for more papers by this authorSandra M. Mooney
Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Search for more papers by this authorSusan M. Smith
Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Search for more papers by this authorCorresponding Author
Nipun Saini
Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Correspondence
Nipun Saini, Nutrition Research Institute, Rm 3111, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC 28081, USA.
Email: [email protected]
Search for more papers by this authorSandra M. Mooney
Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Search for more papers by this authorSusan M. Smith
Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
Search for more papers by this authorAbstract
Prenatal alcohol exposure (PAE) impairs fetal growth and neurodevelopment. Although alcohol is well known to alter metabolism, its impact on these processes during pregnancy is largely unexplored. Here, we investigate how alcohol affects maternal–fetal glucose metabolism using our established mouse binge model of PAE. In the dam, alcohol reduces the hepatic abundance of glucose and glycolytic intermediates, and the gluconeogenic enzymes glucose-6-phosphtase and phosphoenolpyruvate carboxykinase. Fasting blood glucose is also reduced. In a healthy pregnancy, elevated maternal gluconeogenesis and insulin resistance ensures glucose availability for the fetus. Glucose and insulin tolerance tests reveal that alcohol impairs the dam's ability to acquire insulin resistance. Alcohol-exposed dams have enhanced glucose clearance (p < .05) in early gestation, after just two days of alcohol, and this persists through late term when fetal glucose needs are maximal. However, maternal plasma insulin levels, hepatic insulin signaling, and the abundance of glucose transporter proteins remain unchanged. In the PAE fetus, the expression of hepatic gluconeogenic genes is elevated, and there is a trend for elevated blood and liver glucose levels. In contrast, fetal brain and placental glucose levels remain low. This reduced maternal fasting glucose, reduced hepatic glucose, and elevated glucose clearance inversely correlated with fetal body and brain weight. Taken together, these data suggest that alcohol blunts the adaptive changes in maternal glucose metabolism that otherwise enhance fetal glucose availability. Compensatory attempts by the fetus to increase glucose pools via gluconeogenesis do not normalize brain glucose. These metabolic changes may contribute to the impaired fetal growth and brain development that typifies PAE.
DISCLOSURES
The authors declare that they have no conflicts of interests.
Open Research
DATA AVAILABILITY STATEMENT
All the processed data are available as manuscript tables/figures or supplementary information.
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