Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-26T08:41:25.594Z Has data issue: false hasContentIssue false
  • English
  • Français

Feeding a protein-restricted diet during pregnancy induces altered epigenetic regulation of peroxisomal proliferator-activated receptor-α in the heart of the offspring

Published online by Cambridge University Press:  05 August 2010

J. L. Slater-Jefferies ,
K. A. Lillycrop ,
P. A. Townsend ,
C. Torrens ,
S. P. Hoile ,
M. A. Hanson  and
G. C. Burdge
J. L. Slater-Jefferies
Affiliation:
Institute of Developmental Sciences, School of Medicine, University of Southampton, Southampton, UK
K. A. Lillycrop
Affiliation:
Development and Cell Biology, School of Biological Sciences, University of Southampton, UK
P. A. Townsend
Affiliation:
Human Genetics Division, School of Medicine, University of Southampton, Southampton, UK
C. Torrens
Affiliation:
Institute of Developmental Sciences, School of Medicine, University of Southampton, Southampton, UK
S. P. Hoile
Affiliation:
Institute of Developmental Sciences, School of Medicine, University of Southampton, Southampton, UK
M. A. Hanson
Affiliation:
Institute of Developmental Sciences, School of Medicine, University of Southampton, Southampton, UK
G. C. Burdge*
Affiliation:
Institute of Developmental Sciences, School of Medicine, University of Southampton, Southampton, UK
*
*Address for correspondence: G. C. Burdge, Institute of Developmental Sciences, School of Medicine, University of Southampton, Southampton, SO16 6YD, UK. (Email g.c.burdge@southampton.ac.uk)
Get access Rights & Permissions [Opens in a new window]

Abstract

Impaired flexibility in the use of substrates for energy production in the heart is implicated in cardiomyopathy. We investigated the effect of maternal protein restriction during pregnancy in rats on the transcription of key genes in cardiac lipid and carbohydrate metabolism in the offspring. Rats were fed protein-sufficient or protein-restricted (PR) diets during pregnancy. Triacylglycerol concentration in adult (day 105) heart was altered by maternal protein intake contingent on post-weaning fat intake and sex. mRNA expression of peroxisomal proliferator-activated receptor (PPAR)-α and carnitine palmitoyltransferase-1 was increased by the maternal PR diet in adult, but not neonatal, offspring. PPARα promoter methylation was lower in adult and neonatal heart from PR offspring. These findings suggest that prenatal nutrition alters the future transcriptional regulation of cardiac energy metabolism in the offspring through changes in epigenetic regulation of specific genes. However, changes in gene functional changes may not be apparent in early life.

Keywords

cardiomyopathyepigeneticheartPPARprotein restriction
Type
Brief Report
Information
Journal of Developmental Origins of Health and Disease , Volume 2 , Issue 4 , August 2011 , pp. 250 - 255
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Factor, SM, Minase, T, Sonnenblick, EH. Clinical and morphological features of human hypertensive-diabetic cardiomyopathy. Am Heart J. 1980; 99, 446–458.CrossRefGoogle ScholarPubMed
2.Bell, DS. Heart failure: the frequent, forgotten, and often fatal complication of diabetes. Diabetes Care. 2003; 26, 2433–2441.Google Scholar
3.Denton, RM, Randle, PJ. Concentrations of glycerides and phospholipids in rat heart and gastrocnemius muscles. Effects of alloxan-diabetes and perfusion. Biochem J. 1967; 104, 416–422.Google Scholar
4.Murthy, VK, Shipp, JC. Accumulation of myocardial triglycerides ketotic diabetes; evidence for increased biosynthesis. Diabetes. 1977; 26, 222–229.CrossRefGoogle ScholarPubMed
5.Rizza, RA, Crass, MF III, Shipp, JC. Effect of insulin treatment in vivo on heart glycerides and glycogen of alloxan-diabetic rats. Metabolism. 1971; 20, 539–543.CrossRefGoogle ScholarPubMed
6.Chiu, HC, Kovacs, A, Ford, DA, et al. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest. 2001; 107, 813–822.CrossRefGoogle ScholarPubMed
7.Finck, BN, Lehman, JJ, Leone, TC, et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest. 2002; 109, 121–130.Google Scholar
8.Watanabe, K, Fujii, H, Takahashi, T, et al. Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with age-dependent cardiac toxicity. J Biol Chem. 2000; 275, 22293–22299.CrossRefGoogle ScholarPubMed
9.Bishop-Bailey, D. Peroxisome proliferator-activated receptors in the cardiovascular system. Br J Pharmacol. 2000; 129, 823–834.Google Scholar
10.Finck, BN, Kelly, DP. Peroxisome proliferator-activated receptor alpha (PPARalpha) signaling in the gene regulatory control of energy metabolism in the normal and diseased heart. J Mol Cell Cardiol. 2002; 34, 1249–1257.CrossRefGoogle ScholarPubMed
11.Shimano, H. SREBPs: physiology and pathophysiology of the SREBP family. FEBS J. 2009; 276, 616–621.Google Scholar
12.Boudina, S, Abel, ED. Diabetic cardiomyopathy revisited. Circulation. 2007; 115, 3213–3223.CrossRefGoogle ScholarPubMed
13.Finck, BN, Han, X, Courtois, M, et al. A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content. Proc Natl Acad Sci U S A. 2003; 100, 1226–1231.Google Scholar
14.Marfella, R, Di, FC, Portoghese, M, et al. Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome. J Lipid Res. 2009; 50, 2314–2323.CrossRefGoogle ScholarPubMed
15.Gluckman, PD, Hanson, MA, Cooper, C, Thornburg, KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008; 359, 61–73.Google Scholar
16.Armitage, JA, Khan, IY, Taylor, PD, Nathanielsz, PW, Poston, L. Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol. 2004; 561, 355–377.CrossRefGoogle ScholarPubMed
17.Burdge, GC, Lillycrop, KA, Jackson, AA, Gluckman, PD, Hanson, MA. The nature of the growth pattern and of the metabolic response to fasting in the rat are dependent upon the dietary protein and folic acid intakes of their pregnant dams and post-weaning fat consumption. Br J Nutr. 2008; 99, 540–549.Google Scholar
18.Lillycrop, KA, Phillips, ES, Jackson, AA, Hanson, MA, Burdge, GC. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr. 2005; 135, 1382–1386.Google Scholar
19.Elmes, MJ, Gardner, DS, Langley-Evans, SC. Fetal exposure to a maternal low-protein diet is associated with altered left ventricular pressure response to ischaemia-reperfusion injury. Br J Nutr. 2007; 98, 93–100.CrossRefGoogle ScholarPubMed
20.Elmes, MJ, McMullen, S, Gardner, DS, Langley-Evans, SC. Prenatal diet determines susceptibility to cardiac ischaemia-reperfusion injury following treatment with diethylmaleic acid and N-acetylcysteine. Life Sci. 2008; 82, 149–155.CrossRefGoogle Scholar
21.Burdge, GC, Wright, P, Jones, AE, Wootton, SA. A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extraction. Br J Nutr. 2000; 84, 781–787.Google Scholar
22.Burdge, GC, Lillycrop, KA, Phillips, ES, et al. Folic acid supplementation during the Juvenile-Pubertal period in rats modifies the phenotype and epigenotype induced by prenatal nutrition. J Nutr. 2009; 139, 1054–1060.CrossRefGoogle ScholarPubMed
23.Rajabi, M, Kassiotis, C, Razeghi, P, Taegtmeyer, H. Return to the fetal gene program protects the stressed heart: a strong hypothesis. Heart Fail Rev. 2007; 12, 331–343.Google Scholar
24.Panadero, M, Herrera, E, Bocos, C. Different sensitivity of PPAR[alpha] gene expression to nutritional changes in liver of suckling and adult rats. Life Sci. 2005; 76, 1061–1072.CrossRefGoogle ScholarPubMed