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We examined the effect of a high-fat diet (HFD) vs. control diet (CD) upon pregestational and gestational wild-type (wt) and glucose transporter (glut)3 heterozygous (glut3) female mice and observed an increase in pregestational body weights, white adiposity (wt > glut3), circulating cholesterol, and high-density lipoproteins, with glucose intolerance in both genotypes. The HFD-exposed offspring displayed reduced birth weight with catch up to CD-fed in wt vs. an increased birth weight persisting as such at weaning by day 21 in glut3 mice. To decipher the mechanism behind this genotype-specific difference in the HFD offspring's phenotype, we first examined placental macronutrient transporters and noted HFD-induced increase in CD36 in wt with no change in other FATPs, sodium-coupled neutral amino acid transporters and system L amino acid transporter in both genotypes. In contrast, while placental Glut1 increased in both the genotypes, only Glut3 increased in the glut3 genotype in response to HFD. Hence, we next assessed glut3 embryonic (ES) cells under differing stressors of low glucose, hypoxia and inhibition of oxidative phosphorylation. Reduced Glut3-mediated glucose uptake in glut3 vs. wt ES cells culminated in deficient growth. We conclude that maternal HFD affects the in utero growth potential of the offspring by altering placental CD36 and Glut1 concentrations. In contrast, a differential effect on placental Glut3 concentrations between glut3 and wt genotypes is evident, with an increase occurring in the glut3 genotype alone. Deficient Glut3 in ES cells interferes with glucose uptake, cell survival and growth being further exaggerated with low glucose, hypoxia and inhibition of oxidative phosphorylation.
This article was published in the following journal.
Name: The Journal of nutritional biochemistry
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A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg).
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