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Maternal low-quality protein diet exerts sex-specific effects on plasma amino acid profile and alters hepatic expression of methyltransferases in adult rat offspring

  • A. Akyol (a1), A. Kabasakal Cetin (a1), A. Gulec (a1), H. Dasgin (a1), A. Ayaz (a1) and I. Onbasilar (a2)...

Abstract

Nutrition during pregnancy and lactation is a critical factor in the development of the offspring. Both protein content and source in maternal diet affect neonatal health, but the long-term effects of maternal low-quality protein diet on the offspring are less clear. This study aimed to examine the effects of maternal low-quality protein diet on offspring’s growth, development, circulating metabolites and hepatic expression of methyltransferases. Virgin Wistar rats were mated at 11 weeks of age. Dams were then maintained on either a chow diet with 20% casein as the control group (C), or a low-quality protein diet with 20% wheat gluten as the experimental group (WG) throughout gestation and lactation. After weaning, all offspring were fed a control chow diet until the age of 20 weeks. Male WG offspring had significantly lower body weight and energy intake, whereas female WG offspring had significantly higher body weight and energy intake when compared with controls. Early life exposure to WG diet had no significant effect on circulating metabolites. However, fasting insulin concentrations and homoeostasis model assessment-insulin resistance were decreased in WG male and female offspring. Maternal low-quality protein diet increased plasma aspartic acid, glutamic acid, histidine, cystathione and decreased lysine in male WG offspring. Conversely, the same amino acids were reduced in female WG offspring. Adult offspring exposed to WG diet had significantly upregulated hepatic DNMT3a and DNMT3b expressions. Our study showed that there were differential effects of maternal poor-quality protein diet upon adult offspring’s metabolism.

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Corresponding author

Address for correspondence: A. Akyol, Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Sihhiye, Ankara 06100, Turkey. E-mail: asli.akyol@hacettepe.edu.tr

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a

Present address: The Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen AB252ZD, UK.

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References

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1. Fleming, TP, Velazquez, MA, Eckert, JJ. Embryos, DOHaD and David Barker. J Dev Orig Health Dis. 2015; 6, 377383.
2. Lumey, LH, Stein, AD, Kahn, HS, Romijn, JA. Lipid profiles in middle-aged men and women after famine exposure during gestation: the Dutch Hunger Winter Families Study. Am J Clin Nutr. 2009; 89, 17371743.
3. Koupil, I, Shestov, DB, Sparén, P, et al. Blood pressure, hypertension and mortality from circulatory disease in men and women who survived the siege of Leningrad. Eur J Epidemiol. 2007; 22, 223234.
4. McMullen, S, Mostyn, A. Animal models for the study of the developmental origins of health and disease. Proc Nutr Soc. 2009; 68, 306320.
5. Smith, CJ, Ryckman, KK. Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome. Diabetes Metab Syndr Obes. 2015; 8, 295302.
6. Langley-Evans, SC. Fetal programming of cardiovascular function through exposure to maternal undernutrition. Proc Nutr Soc. 2001; 60, 505513.
7. Dunford, LJ, Sinclair, KD, Kwong, WY, et al. Maternal protein-energy malnutrition during early pregnancy in sheepimpacts the fetal ornithine cycle to reduce fetal kidney microvascular development. FASEB J. 2014; 28, 48804892.
8. Lloyd, LJ, Foster, T, Rhodes, P, Rhind, SM, Gardner, DS. Protein-energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function. J Physiol. 2012; 590, 377393.
9. Dumortier, O, Blondeau, B, Duvillié, B, et al. Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet. Diabetologia. 2007; 50, 24952503.
10. Marwarha, G, Claycombe-Larson, K, Schommer, J, Ghribi, O. Maternal low-protein diet decreases brain-derived neurotrophic factor expression in the brains of the neonatal rat offspring. J Nutr Biochem. 2017; 45, 5466.
11. Jia, Y, Cong, R, Li, R, et al. Maternal low-protein diet induces gender-dependent changes in epigenetic regulation of the glucose-6-phosphatase gene in newborn piglet liver. J Nutr. 2012; 142, 16591665.
12. Rodríguez-Trejo, A, Ortiz-López, MG, Zambrano, E, et al. Developmental programming of neonatal pancreatic β-cells by a maternal low-protein diet in rats involves a switch from proliferation to differentiation. Am J Physiol Endocrinol Metab. 2012; 302, E1431E1439.
13. de Brito Alves, JL, de Oliveira, JM, Ferreira, DJ, et al. Maternal protein restriction induced-hypertension is associated to oxidative disruption at transcriptional and functional levels in the medulla oblongata. Clin Exp Pharmacol Physiol. 2016; 43, 11771184.
14. Han, R, Li, A, Li, L, Kitlinska, JB, Zukowska, Z. Maternal low-protein diet up-regulates the neuropeptide Y system in visceral fat and leads to abdominal obesity and glucose intolerance in a sex- and time-specific manner. FASEB J. 2012; 26, 35283536.
15. Qasem, RJ, Cherala, G, D’mello, AP. Maternal protein restriction during pregnancy and lactation in rats imprints long-term reduction in hepatic lipid content selectively in the male offspring. Nutr Res. 2010; 30, 410417.
16. Desai, M, Jellyman, JK, Ross, MG. Epigenomics, gestational programming and risk of metabolic syndrome. Int J Obes (Lond). 2015; 39, 633641.
17. Lillycrop, KA, Burdge, GC. Maternal diet as a modifier of offspring epigenetics. J Dev Orig Health Dis. 2015; 6, 8895.
18. Zeng, Y, Gu, P, Liu, K, Huang, P. Maternal protein restriction in rats leads to reduced PGC-1α expression via altered DNA methylation in skeletal muscle. Mol Med Rep. 2013; 7, 306312.
19. 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.
20. Kato, Y, Kaneda, M, Hata, K, et al. Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse. Hum Mol Genet. 2007; 16, 22722280.
21. Rutherfurd, SM, Fanning, AC, Miller, BJ, Moughan, PJ. Protein digestibility-corrected amino acid scores and digestible indispensable amino acid scores differentially describe protein quality in growing male rats. J Nutr. 2015; 145, 372379.
22. Bozzini, CE, Champin, GM, Alippi, RM, Bozzini, C. Biomechanical properties of the mandible, as assessed by bending test, in rats fed a low-quality protein. Arch Oral Biol. 2013; 58, 427434.
23. Alippi, RM, Picasso, E, Huygens, P, Bozzini, CE, Bozzini, C. Growth-dependent effects of dietary protein concentration and quality on the biomechanical properties of the diaphyseal rat femur. Endocrinol Nutr. 2012; 59, 3543.
24. Hoffman, JR, Falvo, MJ. Protein – Which is best? J Sports Sci Med. 2004; 3, 118130.
25. Gilani, GS, Cockell, KA, Sepehr, E. Effects of antinutritional factors on protein digestibility and amino acid availability in foods. J AOAC Int. 2005; 88, 967987.
26. Kabasakal Cetin, A, Dasgin, H, Gülec, A, Onbasilar, İ, Akyol, A. Maternal low quality protein diet alters plasma amino acid concentrations of weaning rats. Nutrients. 2015; 7, 98479859.
27. Aristoy, MC, Toldra, F. Deproteinization techniques for HPLC amino acid analysis in fresh pork muscle and dry-cured ham. J Agric Food Chem. 1991; 39, 17921795.
28. Antoine, F, Wei, C, Littell, R, Marshall, M. HPLC method for analysis of free amino acids in fish using o-phthaldialdehyde precolumn derivatization. J Agric Food Chem. 1999; 47, 51005107.
29. Badawy, AA, Morgan, CJ, Turner, JA. Application of the phenomenex EZ:faasttrade mark amino acid analysis kit for rapid gas-chromatographic determination of concentrations of plasma tryptophan and its brain uptake competitors. Amino Acids. 2008; 34, 587596.
30. Livak, KJ, Schmittgen, TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25, 402408.
31. Sarwar Gilani, G, Wu Xiao, C, Cockell, KA. Impact of antinutritional factors in food proteins on the digestibility of protein and the bioavailability of amino acids and on protein quality. Br J Nutr. 2012; 108(Suppl. 2), S315S332.
32. Lee, WL, Tsui, KH, Wang, PH. Is nutrition deficiency a key factor of adverse outcomes for pregnant adolescents? J Chin Med Assoc. 2016; 79, 301303.
33. Uauy, R, Suri, DJ, Ghosh, S, Kurpad, A, Rosenberg, IH. Low circulating amino acids and protein quality: an interesting piece in the puzzle of early childhood stunting. EBioMedicine. 2016; 8, 2829.
34. da Silva Aragão, R, Guzmán-Quevedo, O, Pérez-García, G, Manhães-de-Castro, R, Bolaños-Jiménez, F. Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring. Br J Nutr. 2014; 112, 328337.
35. da Silva, AA, Oliveira, MM, Cavalcante, TC, et al. Low protein diet during gestation and lactation increases food reward seeking but does not modify sucrose taste reactivity in adult female rats. Int J Dev Neurosci. 2016; 49, 5059.
36. Qasem, RJ, Li, J, Tang, HM, Pontiggia, L, D’mello, AP. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring. Clin Exp Pharmacol Physiol. 2016; 43, 494502.
37. Jahan-Mihan, A, Smith, CE, Anderson, GH. Effect of protein source in diets fed during gestation and lactation on food intake regulation in male offspring of Wistar rats. Am J Physiol Regul Integr Comp Physiol. 2011; 300, R1175R1184.
38. Zambrano, E, Bautista, CJ, Deás, M, et al. A low maternal protein diet during pregnancy and lactation has sex- and window of exposure-specific effects on offspring growth and food intake, glucose metabolism and serum leptin in the rat. J Physiol. 2006; 571, 221230.
39. Bellinger, L, Sculley, DV, Langley-Evans, SC. Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats. Int J Obes (Lond). 2006; 30, 729738.
40. Qasem, RJ, Li, J, Tang, HM, et al. Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: role of hepatic triglyceride utilization. Clin Exp Pharmacol Physiol. 2015; 42, 380388.
41. Sohi, G, Marchand, K, Revesz, A, Arany, E, Hardy, DB. Maternal protein restriction elevates cholesterol in adult rat offspring due to repressive changes in histone modifications at the cholesterol 7alpha-hydroxylase promoter. Mol Endocrinol. 2011; 25, 785798.
42. Won, SB, Han, A, Kwon, YH. Maternal consumption of low-isoflavone soy protein isolate alters hepatic gene expression and liver development in rat offspring. J Nutr Biochem. 2017; 42, 5161.
43. Erhuma, A, Salter, AM, Sculley, DV, Langley-Evans, SC, Bennett, AJ. Prenatal exposure to a low-protein diet programs disordered regulation of lipid metabolism in the aging rat. Am J Physiol Endocrinol Metab. 2007; 292, E1702E1714.
44. Reeves, PG, Nielsen, FH, Fahey, GC Jr. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr. 1993; 123, 19391951.
45. Teodoro, GF, Vianna, D, Torres-Leal, FL, et al. Leucine is essential for attenuating fetal growth restriction caused by a protein-restricted diet in rats. J Nutr. 2012; 142, 924930.
46. Bourdon, A, Parnet, P, Nowak, C, et al. L-citrulline supplementation enhances fetal growth and protein synthesis in rats with intrauterine growth restriction. J Nutr. 2016; 146, 532541.
47. Shimomura, A, Matsui, I, Hamano, T, et al. Dietary L-lysine prevents arterial calcification in adenine-induced uremic rats. J Am Soc Nephrol. 2014; 25, 19541965.
48. Jimenez-Morales, D, Adamian, L, Shi, D. Lysine carboxylation: unveiling a spontaneous post-translational modification. Acta Crystallogr D Biol Crystallogr. 2014; 70, 4857.
49. You, L, Nie, J, Sun, WJ, Zheng, ZQ, Yang, XJ. Lysine acetylation: enzymes, bromodomains and links to different diseases. Essays Biochem. 2012; 52, 112.
50. Mattocks, DA, Mentch, SJ, Shneyder, J, et al. Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice. Exp Gerontol. 2017; 88, 18.
51. van der Wijst, MG, Venkiteswaran, M, Chen, H, et al. Local chromatin microenvironment determines DNMT activity: from DNA methyltransferase to DNA demethylase or DNA dehydroxymethylase. Epigenetics. 2015; 10, 671676.
52. Ji, Y, Wu, Z, Dai, Z, et al. Nutritional epigenetics with a focus on amino acids: implications for the development and treatment of metabolic syndrome. J Nutr Biochem. 2016; 27, 18.
53. Kolodkin, MH, Auger, AP. Sex difference in the expression of DNA methyltransferase 3a in the rat amygdala during development. J Neuroendocrinol. 2011; 23, 577583.
54. Gong, L, Pan, YX, Chen, H. Gestational low protein diet in the rat mediates Igf2 gene expression in male offspring via altered hepatic DNA methylation. Epigenetics. 2010; 5, 619626.
55. Zhang, N. Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals. Anim Nutr. 2015; 1, 144151.
56. Aiken, CE, Ozanne, SE. Sex differences in developmental programming models. Reproduction. 2013; 145, R1R13.
57. Gallou-Kabani, C, Gabory, A, Tost, J, et al. Sex- and diet-specific changes of imprinted gene expression and DNA methylation in mouse placenta under a high-fat diet. PLoS One. 2010; 5, e14398.

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