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This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/R1455    most recent 91019.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chan, L. L. Y. Articles by Gardner, D. S. Search for Related Content PubMed PubMed Citation Articles by Chan, L. L. Y. Articles by Gardner, D. S.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Effect of maternal nutrient restriction from early to midgestation on cardiac function and metabolism after adolescent-onset obesity

¹School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington; and ²Division of Human Development, School of Clinical Sciences, Queens Medical Centre, Nottingham, United Kingdom

Submitted 16 December 2008 ; accepted in final form 24 February 2009

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 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- (PPAR) and its coactivator (PGC)-1, acetyl-CoA carboxylase (ACC), AMP-activated protein kinase (AMPK)-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-1, AMPK₂, VDAC1, and ACC and increased expression of PPAR and FABP3. However, although NR animals were similarly obese, their transcript expression of ACC, PPAR, 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.

lipid infiltration; hypotensive challenge; myocardial energy metabolism; ectopic lipid deposition; insulin resistance