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Effect of maternal nutrient restriction from early to midgestation on cardiac function and metabolism after
L L Y Chan1, S P Sébert, M A Hyatt
1School of Veterinary Medicine & Science, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD, UK.
Insights
Maternal nutrient restriction in early pregnancy alters offspring heart metabolism and lipid deposition. This increases heart disease risk in obese offspring, potentially leading to earlier heart failure.
Area of Science:
- Cardiovascular Science
- Developmental Biology
- Metabolic Disorders
Background:
- Maternal nutrient restriction (NR) during gestation impacts offspring endocrine sensitivity and organ function.
- Early life nutrition can influence long-term metabolic health and disease susceptibility.
- Obesity is a major risk factor for cardiovascular disease.
Purpose of the Study:
- To investigate if maternal NR alters myocardial energy metabolism and cardiac function in obese adult offspring.
- To determine the effects of NR and an obesogenic environment on gene expression related to cardiac energy metabolism.
- To explore the hypothesis that maternal NR modifies cardiovascular disease risk in obese offspring.
Main Methods:
- Pregnant sheep underwent nutrient restriction (50% energy) or control feeding (100% energy) during early-midgestation.
- Offspring were exposed to an obesogenic environment or remained lean post-weaning.
- Cardiac function, hemodynamic responses to hypotension, and left ventricular gene expression (FABP3, PPARgamma, PGC-1alpha, ACC, AMPK-alpha(2), VDAC1) were assessed at ~1 year of age.
Main Results:
- Obesity induced left ventricular hypertrophy and increased myocardial lipid deposition in NR offspring.
- Obesity reduced expression of PGC-1alpha, AMPK-alpha(2), VDAC1, and ACC, while increasing PPARgamma and FABP3.
- NR offspring, despite obesity, showed normalized expression of ACC, PPARgamma, and FABP3, indicating altered cardiac energy metabolism.
- Obese NR offspring exhibited blunted tachycardia and amplified inotropic response to hypotension.
Conclusions:
- Maternal NR during early organogenesis alters myocardial energy metabolism and lipid handling in adult offspring.
- These alterations may increase susceptibility to cardiac dysfunction and heart failure in obese individuals.
- Early life nutritional programming has lasting effects on cardiovascular health in the context of obesity.
Abstract:
Maternal nutrient restriction (NR) from early to midgestation has marked effects on endocrine sensitivity and organ function of the resulting offspring. We hypothesized that early NR may reset the expression profile of genes central to myocardial energy metabolism, influencing ectopic lipid deposition and cardiac function in the obese adult offspring. NR offspring were exposed to an "obesogenic" environment, and their cardiac function and molecular indexes of myocardial energy metabolism were assessed to explore the hypothesis that an obese individual's risk of heart disease may be modified after maternal NR. Pregnant sheep were fed 100% (control) or 50% (NR) energy requirement from days 30 to 80 of gestation and 100% energy requirement thereafter. At weaning, offspring were exposed to an obesogenic environment or remained lean. At approximately 1 yr of age, the hemodynamic response of these offspring to hypotension, together with left ventricular expression profiles of fatty acid-binding protein 3 (FABP3), peroxisome proliferator-activated receptor-gamma (PPARgamma) and its coactivator (PGC)-1alpha, acetyl-CoA carboxylase (ACC), AMP-activated protein kinase (AMPK)-alpha(2), and voltage-dependent anion channel 1 (VDAC1), was determined. Obesity produced left ventricular hypertrophy in all animals, with increased ectopic (myocardial) lipid in NR offspring. Obesity per se significantly reduced myocardial transcript expression of PGC-1alpha, AMPKalpha(2), VDAC1, and ACC and increased expression of PPARgamma and FABP3. However, although NR animals were similarly obese, their transcript expression of ACC, PPARgamma, and FABP3 was similar to that of lean animals, indicating altered cardiac energy metabolism. Indeed, blunted tachycardia and an amplified inotropic response to hypotension characterized cardiac function in obese NR offspring. The results suggest that maternal NR during early organogenesis can precipitate an altered myocardial response to hypotension and increased myocardial lipid deposition in the adult offspring after adolescent-onset obesity, potentially rendering these individuals more at risk of early heart failure as they age.
