The Programming of Cardiac Hypertrophy in the Offspring by Maternal Obesity Is Associated with Hyperinsulinemia, AKT, ERK, and mTOR Activation
| Autor: | Roger Foo, Heather L. Blackmore, Christine M. Cross, Susan E. Ozanne, Lee Siggens, Denise S. Fernandez-Twinn, Dino A. Giussani |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Offspring medicine.medical_treatment Mothers Cardiomegaly 030204 cardiovascular system & hematology Biology Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Overnutrition Insulin resistance Pregnancy Hyperinsulinism Internal medicine Lactation medicine Hyperinsulinemia Animals Obesity Extracellular Signal-Regulated MAP Kinases 030304 developmental biology 2. Zero hunger 0303 health sciences TOR Serine-Threonine Kinases Insulin Body Weight Renal-Cardiac-Vascular Maternal Nutritional Physiological Phenomena medicine.disease Mice Inbred C57BL Oxidative Stress Phenotype medicine.anatomical_structure Prenatal Exposure Delayed Effects Body Composition Pregnancy Animal Female Lipid Peroxidation Proto-Oncogene Proteins c-akt |
| Zdroj: | Endocrinology |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2012-1508 |
| Popis: | 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(βMHC-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(p67phox) 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. |
| Databáze: | OpenAIRE |
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