The programming of cardiac hypertrophy in the offspring by maternal obesity is associated with hyperinsulinemia, AKT, ERK, and mTOR activation.
Endocrinology
; 153(12): 5961-71, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23070543
ABSTRACT
Human and animal studies suggest that suboptimal early nutrition during critical developmental periods impacts long-term health. For example, maternal overnutrition during pregnancy and lactation in mice programs insulin resistance, obesity, and endothelial dysfunction in the offspring. Here we investigated the effects of diet-induced maternal obesity on the offspring cardiac phenotype and explored potential underlying molecular mechanisms. Dams fed the obesogenic diet were heavier (P < 0.01) and fatter (P < 0.0001) than controls throughout pregnancy and lactation. There was no effect of maternal obesity on offspring body weight or body composition up to 8 wk of age. However, maternal obesity resulted in increased offspring cardiac mass (P < 0.05), increased heart-body weight (P < 0.01), heart weight-tibia length (P < 0.05), increased left ventricular free wall thickness and area (P < 0.01 and P < 0.05, respectively), and increased myocyte width (P < 0.001). Consistent with these structural changes, the expression of molecular markers of cardiac hypertrophy were also increased [Nppb(BNP), Myh7-Myh6(ßMHC-αMHC) (both P < 0.05) and mir-133a (P < 0.01)]. Offspring were hyperinsulinemic and displayed increased insulin action through AKT (P < 0.01), ERK (P < 0.05), and mammalian target of rapamycin (P < 0.05). p38MAPK phosphorylation was also increased (P < 0.05), suggesting pathological remodeling. Increased Ncf2(p67(phox)) expression (P < 0.05) and impaired manganese superoxide dismutase levels (P < 0.01) suggested oxidative stress, which was consistent with an increase in levels of 4-hydroxy-2-trans-nonenal (a measure of lipid peroxidation). We propose that maternal diet-induced obesity leads to offspring cardiac hypertrophy, which is independent of offspring obesity but is associated with hyperinsulinemia-induced activation of AKT, mammalian target of rapamycin, ERK, and oxidative stress.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cardiomegalia
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MAP Quinases Reguladas por Sinal Extracelular
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Proteínas Proto-Oncogênicas c-akt
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Serina-Treonina Quinases TOR
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Hiperinsulinismo
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Obesidade
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article