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Increased systolic blood pressure in rat offspring following a maternal low-protein diet is normalized by maternal dietary choline supplementation

Published online by Cambridge University Press:  25 April 2012

S. Y. Bai
Affiliation:
Liggins Institute and the National Research Centre for Growth and Development, University of Auckland, Auckland, New Zealand
D. I. Briggs
Affiliation:
Liggins Institute and the National Research Centre for Growth and Development, University of Auckland, Auckland, New Zealand
M. H. Vickers*
Affiliation:
Liggins Institute and the National Research Centre for Growth and Development, University of Auckland, Auckland, New Zealand
*
*Address for correspondence: M. H. Vickers, PhD, Liggins Institute and the National Research Centre for Growth and Development, University of Auckland, 1142 Auckland, New Zealand. Email m.vickers@auckland.ac.nz

Abstract

An adverse prenatal environment may induce long-term metabolic consequences, in particular hypertension and cardiovascular disease. A maternal low-protein (LP) diet is well known to result in increased blood pressure (BP) in offspring. Choline has been shown to have direct BP-reducing effects in humans and animals. It has been suggested that endogenous choline synthesis via phosphatidylcholine is constrained during maternal LP exposure. The present study investigates the effect of choline supplementation to mothers fed a LP diet during pregnancy on systolic BP (SBP) in offspring as measured by tail-cuff plethysmography. Wistar rats were assigned to one of three diets to be fed ad libitum throughout pregnancy: (1) control diet (CONT, 20% protein); (2) an LP diet (9% protein); and (3) LP supplemented with choline (LP + C). Dams were fed the CONT diet throughout lactation and offspring were fed the CONT diet from weaning for the remainder of the trial. At postnatal day 150, SBP and retroperitoneal fat mass was significantly increased in LP offspring compared with CONT animals and was normalized in LP + C offspring. Effects of LP + C reduction in SBP were similar in both males and females. Plasma choline and phosphatidylcholine concentrations were not different across treatment groups, but maternal choline supplementation resulted in a significant reduction in homocysteine concentrations in LP + C offspring compared with LP and CONT animals. The present trial shows for the first time that maternal supplementation with dietary choline during periods of LP exposure can normalize increased SBP and fat mass observed in offspring in later life.

Type
Original Article
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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References

1. Nuyt, AM. Mechanisms underlying developmental programming of elevated blood pressure and vascular dysfunction: evidence from human studies and experimental animal models. Clin Sci (Lond). 2008; 114, 117.CrossRefGoogle ScholarPubMed
2. Gardner, DS, Bell, RC, Symonds, ME. Fetal mechanisms that lead to later hypertension. Curr Drug Targets. 2007; 8, 894905.CrossRefGoogle ScholarPubMed
3. Gluckman, PD, Lillycrop, KA, Vickers, MH, et al. . Metabolic plasticity during mammalian development is directionally dependent on early nutritional status. Proc Natl Acad Sci U S A. 2007; 104, 1279612800.CrossRefGoogle ScholarPubMed
4. Gluckman, PD, Hanson, MA, Spencer, HG. Predictive adaptive responses and human evolution. Trends Ecol Evol. 2005; 20, 527533.CrossRefGoogle ScholarPubMed
5. Langley-Evans, SC. Fetal programming of cardiovascular function through exposure to maternal undernutrition. Proc Nutr Soc. 2001; 60, 505513.CrossRefGoogle ScholarPubMed
6. Torrens, C, Poston, L, Hanson, MA. Transmission of raised blood pressure and endothelial dysfunction to the F2 generation induced by maternal protein restriction in the F0, in the absence of dietary challenge in the F1 generation. Br J Nutr. 2008; 100, 760766.CrossRefGoogle Scholar
7. Jackson, AA, Dunn, RL, Marchand, MC, Langley-Evans, SC. Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine. Clin Sci (Lond). 2002; 103, 633639.CrossRefGoogle ScholarPubMed
8. Torrens, C, Brawley, L, Anthony, FW, et al. . Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction. Hypertension. 2006; 47, 982987.CrossRefGoogle ScholarPubMed
9. Langley-Evans, SC, Langley-Evans, AJ, Marchand, MC. Nutritional programming of blood pressure and renal morphology. Arch Physiol Biochem. 2003; 111, 816.CrossRefGoogle ScholarPubMed
10. McMullen, S, Langley-Evans, SC. Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R85R90.CrossRefGoogle ScholarPubMed
11. 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, 93100.CrossRefGoogle ScholarPubMed
12. Cambonie, G, Comte, B, Yzydorczyk, C, et al. . Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R1236R1245.CrossRefGoogle ScholarPubMed
13. Strecker, A. Uber einige neue bestandtheile der schweingalle. Ann Chem Pharmacie. 1862; 123, 353360.CrossRefGoogle Scholar
14. Sanders, LM, Zeisel, SH. Choline: dietary requirements and role in brain development. Nutr Today. 2007; 42, 181186.CrossRefGoogle ScholarPubMed
15. Zeisel, SH. Choline: critical role during fetal development and dietary requirements in adults. Annu Rev Nutr. 2006; 26, 229250.CrossRefGoogle ScholarPubMed
16. Zeisel, SH. Nutritional genomics: defining the dietary requirement and effects of choline. J Nutr. 2011; 141, 531534.CrossRefGoogle ScholarPubMed
17. Kratzing, CC, Perry, JJ. Hypertension in young rats following choline deficiency in maternal diets. J Nutr. 1971; 101, 16571661.CrossRefGoogle ScholarPubMed
18. Konstantinova, SV, Tell, GS, Vollset, SE, et al. . Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women. J Nutr. 2008; 138, 914920.CrossRefGoogle ScholarPubMed
19. Meigs, JB, Jacques, PF, Selhub, J, et al. . Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study. Diabetes Care. 2001; 24, 14031410.CrossRefGoogle ScholarPubMed
20. Vickers, MH, Ikenasio, BA, Breier, BH. Adult growth hormone treatment reduces hypertension and obesity induced by an adverse prenatal environment. J Endocrinol. 2002; 175, 615623.CrossRefGoogle ScholarPubMed
21. Vickers, MH, Ikenasio, BA, Breier, BH. IGF-I treatment reduces hyperphagia, obesity, and hypertension in metabolic disorders induced by fetal programming. Endocrinology. 2001; 142, 39643973.CrossRefGoogle ScholarPubMed
22. Whitesall, SE, Hoff, JB, Vollmer, AP, D'Alecy, LG. Comparison of simultaneous measurement of mouse systolic arterial blood pressure by radiotelemetry and tail-cuff methods. Am J Physiol Heart Circ Physiol. 2004; 286, H2408H2415.CrossRefGoogle ScholarPubMed
23. Lonati, S, Novembrino, C, Ippolito, S, et al. . Analytical performance and method comparison study of the total homocysteine fluorescence polarization immunoassay (FPIA) on the AxSYM analyzer. Clin Chem Lab Med. 2004; 42, 228234.CrossRefGoogle ScholarPubMed
24. Pinotti, L, Baldi, A, Dell'orto, V. Comparative mammalian choline metabolism with emphasis on the high-yielding dairy cow. Nutr Res Rev. 2002; 15, 315332.CrossRefGoogle ScholarPubMed
25. Langley-Evans, SC. Critical differences between two low protein diet protocols in the programming of hypertension in the rat. Int J Food Sci Nutr. 2000; 51, 1117.CrossRefGoogle ScholarPubMed
26. Puddu, M, Fanos, V, Podda, F, Zaffanello, M. The kidney from prenatal to adult life: perinatal programming and reduction of number of nephrons during development. Am J Nephrol. 2009; 30, 162170.CrossRefGoogle ScholarPubMed
27. Woods, LL. Maternal nutrition and predisposition to later kidney disease. Curr Drug Targets. 2007; 8, 906913.CrossRefGoogle ScholarPubMed
28. Vickers, MH, Breier, BH, Cutfield, WS, Hofman, PL, Gluckman, PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab. 2000; 279, E83E87.CrossRefGoogle ScholarPubMed
29. Sahajpal, V, Ashton, N. Renal function and angiotensin AT1 receptor expression in young rats following intrauterine exposure to a maternal low-protein diet. Clin Sci (Lond). 2003; 104, 607614.CrossRefGoogle ScholarPubMed
30. Woods, LL, Ingelfinger, JR, Nyengaard, JR, Rasch, R. Maternal protein restriction suppresses the newborn renin–angiotensin system and programs adult hypertension in rats. Pediatr Res. 2001; 49, 460467.CrossRefGoogle ScholarPubMed
31. Hall, JE. The kidney, hypertension, and obesity. Hypertension. 2003; 41, 625633.CrossRefGoogle ScholarPubMed
32. McMullen, S, Langley-Evans, SC. Sex-specific effects of prenatal low-protein and carbenoxolone exposure on renal angiotensin receptor expression in rats. Hypertension. 2005; 46, 13741380.CrossRefGoogle ScholarPubMed
33. Marin, MC, De Tomas, ME, Serres, C, Mercuri, O. Protein-energy malnutrition during gestation and lactation in rats affects growth rate, brain development and essential fatty acid metabolism. J Nutr. 1995; 125, 10171024.Google ScholarPubMed
34. Chen, CM, Wang, LF, Su, B. Effects of maternal undernutrition during late gestation on the lung surfactant system and morphometry in rats. Pediatr Res. 2004; 56, 329335.CrossRefGoogle ScholarPubMed
35. Desai, M, Crowther, NJ, Lucas, A, Hales, CN. Organ-selective growth in the offspring of protein-restricted mothers. Br J Nutr. 1996; 76, 591603.CrossRefGoogle ScholarPubMed
36. Ashfield-Watt, PA, Moat, SJ, Doshi, SN, McDowell, IF. Folate, homocysteine, endothelial function and cardiovascular disease. What is the link? Biomed Pharmacother. 2001; 55, 425433.CrossRefGoogle ScholarPubMed
37. Sorensen, A, Mayntz, D, Raubenheimer, D, Simpson, SJ. Protein-leverage in mice: the geometry of macronutrient balancing and consequences for fat deposition. Obesity (Silver Spring). 2008; 16, 566571.CrossRefGoogle ScholarPubMed
38. Simpson, SJ, Raubenheimer, D. Obesity: the protein leverage hypothesis. Obes Rev. 2005; 6, 133142.CrossRefGoogle ScholarPubMed
39. Fernandez-Figares, I, Wray-Cahen, D, Steele, NC, et al. . Effect of dietary betaine on nutrient utilization and partitioning in the young growing feed-restricted pig. J Anim Sci. 2002; 80, 421428.CrossRefGoogle Scholar
40. Hongu, N, Sachan, DS. Carnitine and choline supplementation with exercise alter carnitine profiles, biochemical markers of fat metabolism and serum leptin concentration in healthy women. J Nutr. 2003; 133, 8489.CrossRefGoogle ScholarPubMed
41. Bogdarina, I, Welham, S, King, PJ, Burns, SP, Clark, AJ. Epigenetic modification of the renin–angiotensin system in the fetal programming of hypertension. Circ Res. 2007; 100, 520526.CrossRefGoogle ScholarPubMed
42. Davison, JM, Mellott, TJ, Kovacheva, VP, Blusztajn, JK. Gestational choline supply regulates methylation of histone H3, expression of histone methyltransferases G9a (Kmt1c) and Suv39h1 (Kmt1a), and DNA methylation of their genes in rat fetal liver and brain. J Biol Chem. 2009; 284, 19821989.CrossRefGoogle ScholarPubMed
43. Lillycrop, KA, Slater-Jefferies, JL, Hanson, MA, et al. . Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br J Nutr. 2007; 97, 10641073.CrossRefGoogle ScholarPubMed
44. Lillycrop, KA, Jackson, AA, Hanson, MA, Burdge, GC. Dietary protein restriction in the pregnant rat induces altered covalent modifications to histones at the glucocorticoid receptor promoter in the liver of the offspring after weaning. Proc Nutr Soc. 2006; 65, 108A.Google Scholar
45. 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, 13821386.CrossRefGoogle ScholarPubMed
46. Nuyt, AM, Szyf, M. Developmental programming through epigenetic changes. Circ Res. 2007; 100, 452455.CrossRefGoogle ScholarPubMed
47. Tonkiss, J, Trzcińska, M, Galler, JR, Ruiz-Opazo, N, Herrera, VL. Prenatal malnutrition-induced changes in blood pressure: dissociation of stress and nonstress responses using radiotelemetry. Hypertension 32, 108114.CrossRefGoogle Scholar