Shared Effects of Genetic and Intrauterine and Perinatal Environment on the Development of Metabolic Syndrome

Patricia M. Vuguin, Kirsten Hartil, Michael Kruse, Harpreet Kaur, Chia Lei Vivian Lin, Ariana Fiallo, Alan Scott Glenn, Avanee Patel, Lyda Williams, Yoshinori Seki, Ellen B. Katz, Maureen J. Charron

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Genetic and environmental factors, including the in utero environment, contribute to Metabolic Syndrome. Exposure to high fat diet exposure in utero and lactation increases incidence of Metabolic Syndrome in offspring. Using GLUT4 heterozygous (G4+/-) mice, genetically predisposed to Type 2 Diabetes Mellitus, and wild-type littermates we demonstrate genotype specific differences to high fat in utero and lactation. High fat in utero and lactation increased adiposity and impaired insulin and glucose tolerance in both genotypes. High fat wild type offspring had increased serum glucose and PAI-1 levels and decreased adiponectin at 6 wks of age compared to control wild type. High fat G4+/- offspring had increased systolic blood pressure at 13 wks of age compared to all other groups. Potential fetal origins of adult Metabolic Syndrome were investigated. Regardless of genotype, high fat in utero decreased fetal weight and crown rump length at embryonic day 18.5 compared to control. Hepatic expression of genes involved in glycolysis, gluconeogenesis, oxidative stress and inflammation were increased with high fat in utero. Fetal serum glucose levels were decreased in high fat G4+/- compared to high fat wild type fetuses. High fat G4+/-, but not high fat wild type fetuses, had increased levels of serum cytokines (IFN-γ, MCP-1, RANTES and M-CSF) compared to control. This data demonstrates that high fat during pregnancy and lactation increases Metabolic Syndrome male offspring and that heterozygous deletion of GLUT4 augments susceptibility to increased systolic blood pressure. Fetal adaptations to high fat in utero that may predispose to Metabolic Syndrome in adulthood include changes in fetal hepatic gene expression and alterations in circulating cytokines. These results suggest that the interaction between in utero-perinatal environment and genotype plays a critical role in the developmental origin of health and disease.

Original languageEnglish (US)
Article numbere63021
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 17 2013

Fingerprint

metabolic syndrome
Fats
lipids
Lactation
lactation
Genotype
Blood Pressure
genotype
systolic blood pressure
Blood pressure
Glucose
fetus
Fetus
cytokines
Serum
Cytokines
Crown-Rump Length
Gene Expression
Chemokine CCL5
gene expression

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Shared Effects of Genetic and Intrauterine and Perinatal Environment on the Development of Metabolic Syndrome. / Vuguin, Patricia M.; Hartil, Kirsten; Kruse, Michael; Kaur, Harpreet; Lin, Chia Lei Vivian; Fiallo, Ariana; Glenn, Alan Scott; Patel, Avanee; Williams, Lyda; Seki, Yoshinori; Katz, Ellen B.; Charron, Maureen J.

In: PLoS One, Vol. 8, No. 5, e63021, 17.05.2013.

Research output: Contribution to journalArticle

Vuguin, PM, Hartil, K, Kruse, M, Kaur, H, Lin, CLV, Fiallo, A, Glenn, AS, Patel, A, Williams, L, Seki, Y, Katz, EB & Charron, MJ 2013, 'Shared Effects of Genetic and Intrauterine and Perinatal Environment on the Development of Metabolic Syndrome', PLoS One, vol. 8, no. 5, e63021. https://doi.org/10.1371/journal.pone.0063021
Vuguin, Patricia M. ; Hartil, Kirsten ; Kruse, Michael ; Kaur, Harpreet ; Lin, Chia Lei Vivian ; Fiallo, Ariana ; Glenn, Alan Scott ; Patel, Avanee ; Williams, Lyda ; Seki, Yoshinori ; Katz, Ellen B. ; Charron, Maureen J. / Shared Effects of Genetic and Intrauterine and Perinatal Environment on the Development of Metabolic Syndrome. In: PLoS One. 2013 ; Vol. 8, No. 5.
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