Abstract
Studies were conducted to determine whether maternal substrate utilization during pregnancy affects fetal growth and predisposes offspring to metabolic disease. Female wild-type (WT) and glucose transporter 4 heterozygous mice (G4±, a model of altered peripheral substrate utilization) were fed high-fat diet (HFD, 35.5% fat) or control chow (C, 9.5% fat) for 2 wk before mating, throughout pregnancy and lactation (IU/L). WT HFD females exhibited increased serum nonesterified fatty acid and lactate levels and increased hepatic mRNA expression of peroxisome proliferator-activated receptor γ coactivator-1-β and SREBP-1c, consistent with increased lipogenesis. G4± HFD females exhibited enhanced lipid clearance, and exposure to HFD did not increase hepatic gene expression. HFD independent of maternal genotype decreased fetal growth and birth weight. WT offspring were weaned onto a low-fat diet (5.6% fat). Male offspring of WT mothers exposed to HFD exhibited “catch-up” growth accompanied by increased adiposity, impaired glucose tolerance, and insulin sensitivity. In contrast, male offspring of G4± HFD mothers did not exhibit any characteristics of metabolic syndrome. These data suggest that differences in maternal substrate utilization influence offspring metabolic phenotype.
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Abbreviations
- BW:
-
body weight
- C:
-
control breeding chow
- CRL:
-
crown-rump length
- e:
-
embryonic day
- G4±:
-
heterozygous deletion of glucose transporter 4
- GLUT4:
-
glucose transporter 4
- GTT:
-
glucose tolerance test
- HFD:
-
high-fat diet
- ITT:
-
insulin tolerance test
- IU:
-
In Utero
- L:
-
lactation
- T2DM:
-
type 2 diabetes mellitus
- TG:
-
triglycerides
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Acknowledgements
The authors thank Dr. Ellen Katz for many helpful discussions and for assistance in revising this manuscript. We also thank the Diabetes Research and Training Center, Albert Einstein College of Medicine for help with the ECHO MRI and LINCOPLEX analysis.
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Supported by grants from the National Institutes of Health R01DK47425, R01HL73163, R01HL58119, R21 DK081194, P50 DK051296, the Diabetes Research and Training program P60-DK020541, and Cancer Centers of Albert Einstein College of Medicine (M.J.C.) and KO8 HD042172, and an Independent Research Award from Pfizer Inc. (P.V.). K.H. was supported by a Mentor-Based Postdoctoral Fellowship awarded to M.J.C. from the American Diabetes Association.
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Hartil, K., Vuguin, P., Kruse, M. et al. Maternal Substrate Utilization Programs the Development of the Metabolic Syndrome in Male Mice Exposed to High Fat I n Utero. Pediatr Res 66, 368–373 (2009). https://doi.org/10.1203/PDR.0b013e3181b33375
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DOI: https://doi.org/10.1203/PDR.0b013e3181b33375
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