Maternal substrate utilization programs the development of the metabolic syndrome in male mice exposed to high fat in utero.
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 gamma coactivator-1-beta 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.
Hartil
Kirsten
K
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Vuguin
Patricia M
PM
Kruse
Michael
M
Schmuel
Esther
E
Fiallo
Ariana
A
Vargas
Carlos
C
Warner
Matthew J
MJ
Durand
Jorge L
JL
Jelicks
Linda A
LA
Charron
Maureen J
MJ
D000818:Animals; D001835:Body Weight; D004041:Dietary Fats / Q000378:metabolism*; D004435:Eating; D005260:Female; D047109:Fetal Development / Q000502:physiology; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D024821:Metabolic Syndrome / Q000378:metabolism*; D051379:Mice; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena
D004041:Dietary Fats; D007328:Insulin; D005947:Glucose