Dataset Information

Maternal high-fat diet impacts endothelial function in nonhuman primate offspring.

ABSTRACT:

Objective

The link between maternal under-nutrition and cardiovascular disease (CVD) in the offspring later in life is well recognized, but the impact of maternal over-nutrition on the offspring's cardiovascular function and subsequent risk for CVD later in life remains unclear. Here, we investigated the impact of maternal exposure to a high-fat/calorie diet (HFD) during pregnancy and early postnatal period on endothelial function of the offspring in a nonhuman primate model.

Methods

Offspring, naturally born to either a control (CTR) diet (14% fat calories) or a HFD (36% fat calories) consumption dam, were breast-fed until weaning at about 8 months of age. After weaning, the offspring were either maintained on the same diet (CTR/CTR, HFD/HFD), or underwent a diet switch (CTR/HFD, HFD/CTR). Blood samples and arterial tissues were collected at necropsy when the animals were about 13 months of age.

Results

HFD/HFD juveniles displayed an increased plasma insulin level and glucose-stimulated insulin secretion in comparison with CTR/CTR. In abdominal aorta, but not the renal artery, acetylcholine-induced vasorelaxation was decreased remarkably for HFD/HFD juveniles compared with CTR/CTR. HFD/HFD animals also showed a thicker intima wall and an abnormal vascular-morphology, concurrent with elevated expression levels of several markers related to vascular inflammation and fibrinolytic function. Diet-switching animals (HFD/CTR and CTR/HFD) displayed modest damage on the abdominal vessel.

Conclusion

Our data indicate that maternal HFD exposure impairs offspring's endothelial function. Both early programming events and postweaning diet contribute to the abnormalities that could be reversed partially by diet intervention.

SUBMITTER: Fan L

PROVIDER: S-EPMC3468685 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A maternal high-fat diet (HFD) has been shown to exert deleterious effects on fetal programming by impairing embryo growth, and exerts a long-term effect on the health of offspring. The present study aimed to evaluate the effect of a maternal HFD on the ovaries of offspring from the perspective of oxidative stress. Female C57BL/6J mice were randomly assigned to four groups fed various HFDs during the preconception (4 weeks) and gestation-lactation periods. Offspring were fed a normal diet after weaning, and serum and ovaries were collected at 10 weeks of age. The developmental status of follicles was observed using hematoxylin and eosin staining. The serum oxidative stress levels and insulin resistance were detected using ELISA test kits. The expression of phosphorylated form of H2AX histone variant (γH2AX), forkhead box protein O3a (FOXO3a), Bcl-2-like protein 11 (Bim)and insulin-like growth factor (IGF)-1 in ovarian tissue was analyzed using reverse transcription-quantitative PCR and western blot analyses to further explore the pathogenic mechanism. Prenatal exposure to a maternal HFD resulted in a reduced number of primordial and preantral follicles in the ovaries of offspring. Exposure to an HFD in the preconception period exerted a greater effect on the offspring compared with exposure to an HFD in the gestation-lactation period. A reduction in fat intake during the preconception, gestation and lactation periods significantly reduced the associated adverse outcomes. The expression of genes (FOXO3a, IGF-1, γH2AX and Bim) involved in oxidative stress showed a decreasing trend (high-fat/high-fat>high-fat/control>control/high-fat >control/control) in the ovaries of offspring. Overall, HFD exposure during the preconception period exerted a greater effect on offspring compared with HFD exposure during the gestation-lactation period. The long-term effect on follicular growth and development may be associated with increased oxidative stress and the activation of the insulin/PI3K/Akt pathway.