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Current Protein & Peptide Science


ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Epigenetic Mechanisms of Maternal Dietary Protein and Amino Acids Affecting Growth and Development of Offspring

Author(s): Yi Wu, Zhibin Cheng*, Yueyu Bai* and Xi Ma*

Volume 20 , Issue 7 , 2019

Page: [727 - 735] Pages: 9

DOI: 10.2174/1389203720666190125110150

Price: $65


Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring’s later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body’s one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.

Keywords: DNA methylation, amino acids, epigenetic mechanism, maternal nutrition, offspring, protein.

Graphical Abstract
Comerford, K.B.; Ayoob, K.T.; Murray, R.D.; Atkinson, S.A. The role of avocados in maternal diets during the periconceptional period, pregnancy, and lactation. Nutrients, 2016, 8, 313.
Li, Y. Epigenetic mechanisms link maternal diets and gut microbiome to obesity in the offspring. Front. Genet., 2018, 9, 342.
Oomen, M.E.; Dekker, J. Epigenetic characteristics of the mitotic chromosome in 1D and 3D. Crit. Rev. Biochem. Mol. Biol., 2017, 52, 185-204.
Jones, M.J.; Goodman, S.J.; Kobor, M.S. DNA methylation and healthy human aging. Aging Cell, 2015, 14, 924-932.
Moody, L.; Chen, H.; Pan, Y.X. Early-life nutritional programming of cognition-the fundamental role of epigenetic mechanisms in mediating the relation between early-life environment and learning and memory process. Adv. Nutr., 2017, 8, 337-350.
Szarc vel Szic, K.; Declerck, K.; Vidaković, M.; Vanden Berghe, W. From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition? Clin. Epigenetics, 2015, 7, 33.
Maslova, E.; Hansen, S.; Grunnet, L.G.; Strøm, M.; Bjerregaard, A.A.; Hjort, L.; Kampmann, F.B.; Madsen, C.M.; Baun Thuesen, A.C.; Bech, B.H.; Halldorsson, T.I.; Vaag, A.A.; Olsen, S.F. Maternal protein intake in pregnancy and offspring metabolic health at age 9-16 y: Results from a Danish cohort of gestational diabetes mellitus pregnancies and controls. Am. J. Clin. Nutr., 2017, 106, 623-636.
Dominguez-Salas, P.; Cox, S.E.; Prentice, A.M.; Hennig, B.J.; Moore, S.E. Maternal nutritional status, C(1) metabolism and offspring DNA methylation: a review of current evidence in human subjects. Proc. Nutr. Soc., 2012, 71, 154-165.
Lonnie, M.; Hooker, E.; Brunstrom, J.M.; Corfe, B.M.; Green, M.A.; Watson, A.W.; Williams, E.A.; Stevenson, E.J.; Penson, S.; Johnstone, A.M. Protein for life: Review of optimal protein intake, sustainable dietary sources and the effect on appetite in ageing adults. Nutrients, 2018, 10, 360.
Pinheiro, D.F.; Pinheiro, P.F.; Buratini, J., Jr; Castilho, A.C.; Lima, P.F.; Trinca, L.A.; Vicentini-Paulino Mde, L. Maternal protein restriction during pregnancy affects gene expression and immunolocalization of intestinal nutrient transporters in rats. Clin. Sci. (Lond.), 2013, 125, 281-289.
Carone, B.R.; Fauquier, L.; Habib, N.; Shea, J.M.; Hart, C.E.; Li, R.; Bock, C.; Li, C.; Gu, H.; Zamore, P.D.; Meissner, A.; Weng, Z.; Hofmann, H.A.; Friedman, N.; Rando, O.J. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell, 2010, 143, 1084-1096.
Meijer, A.J.; Lorin, S.; Blommaart, E.F.; Codogno, P. Regulation of autophagy by amino acids and MTOR-dependent signal transduction. Amino Acids, 2015, 47, 2037-2063.
Souza, A.L.; Fiorini Aguiar, S.L.; Gonçalves Miranda, M.C.; Lemos, L.; Freitas Guimaraes, M.A.; Reis, D.S.; Vieira Barros, P.A.; Veloso, E.S.; Carvalho, T.G.; Ribeiro, F.M.; Ferreira, E.; Cara, D.C.; Gomes-Santos, A.C.; Faria, A.M.C. Consumption of diet containing free amino acids exacerbates colitis in mice. Front. Immunol., 2017, 8, 1587.
Reidy, P.T.; Rasmussen, B.B. Role of ingested amino acids and protein in the promotion of resistance exercise-induced muscle protein anabolism. J. Nutr., 2016, 146, 155-183.
Wu, Ct.; Morris, J.R. Genes, genetics, and epigenetics: A correspondence. Science, 2001, 293, 1103-1105.
Suzuki, M.M.; Bird, A. DNA methylation landscapes: Provocative insights from epigenomics. Nat. Rev. Genet., 2008, 9, 465-476.
Maunakea, A.K.; Chepelev, I.; Cui, K.; Zhao, K. Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition. Cell Res., 2013, 23, 1256-1269.
Sati, S.; Tanwar, V.S.; Kumar, K.A.; Patowary, A.; Jain, V.; Ghosh, S.; Ahmad, S.; Singh, M.; Reddy, S.U.; Chandak, G.R.; Raghunath, M.; Sivasubbu, S.; Chakraborty, K.; Scaria, V.; Sengupta, S. High resolution methylome map of rat indicates role of intragenic DNA methylation in identification of coding region. PLoS One, 2012, 7e31621
McGee, M.; Bainbridge, S.; Fontaine-Bisson, B. A crucial role for maternal dietary methyl donor intake in epigenetic programming and fetal growth outcomes. Nutr. Rev., 2018, 76, 469-478.
Padmanabhan, N.; Watson, E.D. Lessons from the one-carbon metabolism:passing it along to the next generation. Reprod. Biomed. Online, 2013, 27, 637-643.
Steegers-Theunissen, R.P.; Twigt, J.; Pestinger, Vn.; Sinclair, K.D. The periconceptional period, reproduction and log-term health of offspring: The importance of one-carbon metabolism. Hum. Reprod. Update, 2013, 19, 640-655.
Barua, S.; Kuizon, S.; Junaid, M.A. Folic acid supplementation in pregnancy and implications in health and disease. J. Biomed. Sci., 2014, 21, 77.
Singh, M.D.; Thomas, P.; Owens, J.; Hague, W.; Fenech, M. Potential role of folate in pre-eclampsia. Nutr. Rev., 2015, 73, 694-722.
Bailey, L.B.; Stover, P.J.; McNulty, H.; Fenech, M.F.; Gregory, J.F.; Mills, J.L.; Pfeiffer, C.M.; Fazili, Z.; Zhang, M.; Ueland, P.M.; Molloy, A.M.; Caudill, M.A.; Shane, B.; Berry, R.J.; Bailey, R.L.; Hausman, D.B.; Raghavan, R.; Raiten, D.J. Biomarkers of nutrition for development-folate review. J. Nutr., 2015, 145, 1636S-1680S.
Leung, K.Y.; Pai, Y.J.; Chen, Q.; Santos, C.; Calvani, E.; Sudiwala, S.; Savery, D.; Ralser, M.; Gross, S.S.; Copp, A.J.; Greene, N.D.E. Partitioning of one-carbon units in folate and methionine metabolism is essential for neural tube closure. Cell Rep., 2017, 21, 1795-1808.
Osorio, J.S.; Jacometo, C.B.; Zhou, Z.; Luchini, D.; Cardoso, F.C.; Loor, J.J. Hepatic global DNA and peroxisome proliferator-activated receptor alpha promoter methylation are altered in peripartal dairy cows fed rumen-protected methionine. J. Dairy Sci., 2016, 99, 234-244.
Mentch, S.J.; Mehrmohamadi, M.; Huang, L.; Liu, X.; Gupta, D.; Mattocks, D.; Gómez Padilla, P.; Ables, G.; Bamman, M.M.; Thalacker-Mercer, A.E.; Nichenametla, S.N.; Locasale, J.W. Histone methylation dynamics and gene regulation occur through the sensing of one-carbon metabolism. Cell Metab., 2015, 22, 861-873.
Ziegler, A.N.; Levison, S.W.; Wood, T.L. Insulin and IGF receptor signaling in neural-stem-cell homeostasis. Nat. Rev. Endocrinol., 2015, 11, 161-170.
Kim, H.W.; Kim, K.N.; Choi, Y.J.; Chang, N. Effects of paternal folate deficiency on the expression of insulin-like growth factor-2 and global DNA methylation in the fetal brain. Mol. Nutr. Food Res., 2013, 57, 671-676.
Cordero, P.; Gomez-Uriz, A.M.; Campion, J.; Milagro, F.I.; Martinez, J.A. Dietary supplementation with methyl donors reduces fatty liver and modifies the fatty acid synthase DNA methylation profile in rats fed an obesogenic diet. Genes Nutr., 2013, 8, 105-113.
Huang, C.; Song, P.; Fan, P.; Hou, C.; Thacker, P.A.; Ma, X. Dietary sodium butyrate decreased postweaning diarrhea by modulating intestinal permeability and changing the bacterial community in weaned piglets. J. Nutr., 2015, 145, 2774-2780.
Breton, C.V.; Siegmund, K.D.; Joubert, B.R.; Wang, X.; Qui, W. Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation. PLoS One, 2014, 9e112422
Buscariollo, D.L.; Fang, X.; Greenwood, V.; Xue, H.; Rivkees, S.A.; Wendler, C.C. Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice. PLoS One, 2014, 9e87547
He, L.; He, T.; Farrar, S.; Ji, L.; Liu, T.; Ma, X. Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell. Physiol. Biochem., 2017, 44, 532-553.
Hake, S.B.; Xiao, A.; Allis, C.D. The language of covalent histone modifications. Nature, 2000, 403, 41-45.
Serani, M.A.; Hayashi, K.; Hajkova, P. Genetic and epigenetic regulators of pluripotency. Cell, 2007, 128, 747-762.
Kouzarides, T. Chromatin modifications and their function. Cell, 2007, 128, 693-705.
Yun, M.Y.; Wu, J.; Workman, J.L.; Li, B. Readers of histone modifications. Cell Res., 2011, 21, 564-578.
Zheng, F.; Kasper, L.H.; Bedford, D.C.; Lerach, S.; Teubner, B.J.W.; Brindle, P.K. Mutation of the CH1 domain in the histone acetyltransferase CREBBP results in autism-relevant behaviors in mice. PLoS One, 2016, 11e0146366
Wang, Y.; Guo, Y.R.; Liu, K.; Yin, Z.; Liu, R.; Xia, Y.; Tan, L.; Yang, P.; Lee, J.H.; Li, X.J.; Hawke, D.; Zheng, Y.; Qian, X.; Lyu, J.; He, J.; Xing, D.; Tao, Y.J.; Lu, Z. KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase. Nature, 2017, 552, 273-277.
Wang, G.L.; Salisbury, E.; Shi, X.; Timchenko, L.; Medrano, E.E.; Timchenko, N.A. HDAC1 cooperates with C/EBPalpha in the inhibition of liver proliferation in old mice. J. Biol. Chem., 2008, 283, 26169-26178.
Ravnskjaer, K.; Hogan, M.F.; Lackey, D.; Tora, L.; Dent, S.Y.R.; Olefsky, J.; Montminy, M. Glucagon regulates gluconeogenesis through KAT2B-and WDR5-mediated epigenetic effects. J. Clin. Invest., 2013, 123, 4318-4328.
Hennighausen, L.; Robinson, G.W. Interpretation of cytokine signaling through the transcription factors STAT5A and STAT5B. Genes Dev., 2008, 22, 711-721.
Cao, J.; Wu, L.; Zhang, S.M.; Lu, M.; Cheung, W.K.; Cai, W.; Gale, M.; Xu, Q.; Yan, Q. An easy and efficient inducible CRISPR/Cas9 platform with improved specificity for multiple gene targeting. Nucleic Acids Res., 2016, 44e149
Rajesh, C. Rao.; Yali, Dou. Hijacked in cancer: the MLL/KMT2 family of methyltransferases. Nat. Rev. Cancer, 2015, 15, 334-346.
Rogakou, E.P.; Nieves-Neira, W.; Boon, C.; Pommier, Y.; Bonner, W.M. Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J. Biol. Chem., 2000, 275, 9390-9395.
Ma, M.K.; Heath, C.; Hair, A.; West, A.G. Histone crosstalk directed by H2B ubiquitination is required for chromatin boundary integrity. PLoS Genet., 2011, 7e1002175
Jiménez-Chillarón, J.C.; Díaz, R.; Martínez, D.; Pentinat, T.; Ramón-Krauel, M.; Ribó, S.; Plösch, T. The role of nutrition on epigenetic modifications and their implications on health. Biochimie, 2012, 94, 2242-2263.
Hake, S.B.; Xiao, A.; Allis, C.D. Linking the epigenetic ‘language’ of covalent histone modifications to cancer. Br. J. Cancer, 2004, 90, 761-769.
Gupta, S.; Kim, S.Y.; Artis, S.; Molfese, D.L.; Schumacher, A.; Sweatt, J.D.; Paylor, R.E.; Lubin, F.D. Histone methylation regulates memory formation. J. Neurosci., 2010, 30, 3589-3599.
Strahl, B.D.; Allis, C.D. The language of covalent histone modifications. Nature, 2000, 403, 41-45.
Liu, D.; Perkins, J.T.; Hennig, B. EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells. J. Nutr. Biochem., 2016, 28, 164-170.
Yun, J.M.; Jialal, I.; Devaraj, S. Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. J. Nutr. Biochem., 2011, 22, 450-458.
Liu, P.; Zhao, J.; Guo, P.; Lu, W.; Geng, Z.; Levesque, C.L.; Johnston, L.J.; Wang, C.; Liu, L.; Zhang, J.; Ma, N.; Qiao, S.; Ma, X. Dietary corn bran fermented by Bacillus subtilis MA139 decreased gut cellulolytic bacteria and microbiota diversity in finishing pigs. Front. Cell. Infect. Microbiol., 2017, 7, 526.
Chen, X.; Song, P.; Fan, P.; He, T.; Jacobs, D.; Levesque, C.L.; Johnston, L.J.; Ji, L.; Ma, N.; Chen, Y.; Zhang, J.; Zhao, J.; Ma, X. Moderate dietary protein restriction optimized gut microbiota and mucosal barrier in growing pig model. Front. Cell. Infect. Microbiol., 2018, 8, 246.
Gerhauser, C. Impact of dietary gut microbial metabolites on the epigenome. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2018, 37320170359
O’Keefe, S.J. Diet, microorganisms and their metabolites, and colon cancer. Nat. Rev. Gastroenterol. Hepatol., 2016, 13, 691-706.
Donohoe, D.R.; Collins, L.B.; Wali, A.; Bigler, R.; Sun, W.; Bultman, S.J. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol. Cell, 2012, 48, 612-626.
Ambros, V.; Ruvkun, G. Recent molecular genetic explorations of Caenorhabditis elegans microRNAs. Genetics, 2018, 209, 651-673.
Rodriguez, A.; Griffiths-Jones, S.; Ashurst, J.L.; Bradley, A. Identification of mammalian microRNA host genes and transcription units. Genome Res., 2004, 14, 1902-1910.
Esquela-Kerscher, A.; Slack, F.J. Oncomirs - microRNAs with a role in cancer. Nat. Rev. Cancer, 2006, 6, 259-269.
Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 2004, 116, 281-297.
Chuang, J.C.; Jones, P.A. Epigenetics and microRNAs. Pediatr. Res., 2007, 61, 24R-29R.
Keller, J.; Ringseis, R. Supplemental carnitine affects the microRNA expression profile in skeletal muscle of obese Zucker rat. BMC Genomics, 2014, 15, 512.
Wang, L.L.; Zhang, Z. Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation. Hum. Reprod., 2009, 24, 562-579.
Berni Canani, R.; Di Costanzo, M. Epigenetic mechanisms elicited by nutrition in early life. Nutrition, 2011, 24, 198-205.
Lucas, A.; Baker, B.A.; Desai, M.; Hales, C.N. Nutrition in pregnant or lactating rats programs lipid metabolism in the offspring. Br. J. Nutr., 1996, 76, 605-612.
Lucas, A. Programming by early nutrition: An experimental approach. J. Nutr., 1998, 128, 401S-406S.
Ma, N.; Guo, P.; Zhang, J.; He, T.; Kim, S.W.; Zhang, G.; Ma, X. Nutrients mediate intestinal bacteria-mucosal immune crosstalk. Front. Immunol., 2018, 9, 5.
Fan, P.; Li, L.; Rezaei, A.; Eslamfam, S.; Che, D.; Ma, X. Metabolites of dietary protein and peptides by intestinal microbes and their impacts on gut. Curr. Protein Pept. Sci., 2015, 16, 646-654.
Fan, P.; Liu, P.; Song, P.; Chen, X.; Ma, X. Moderate dietary protein restriction alters the composition of gut microbiota and improves ileal barrier function in adult pig model. Sci. Rep., 2017, 7, 43412.
Reamon-Buettner, S.M.; Buschmann, J.; Lewin, G. Identifying placental epigenetic alterations in an intrauterine growth restriction (IUGR) rat model induced by gestational protein deficiency. Reprod. Toxicol., 2014, 45, 117-124.
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, 54-66.
Claycombe, K.J.; Uthus, E.O.; Roemmich, J.N.; Johnson, L.K.; Johnson, W.T. Prenatal low-protein and postnatal high-fat diets induce rapid adipose tissue growth by inducing Igf2 expression in Sprague Dawley rat offspring. J. Nutr., 2013, 143, 1533-1539.
Sosa-Larios, T.C.; Milliar-Garcia, A.; Reyes-Castro, L.A.; Morimoto, S.; Jaramillo-Flores, M.E. Retraction: Alterations in lipid metabolism due to a protein-restricted diet in rats during gestation and/or lactation. Food Funct., 2018, 9, 1274.
Galmozzi, A.; Sonne, S.B.; Altshuler-Keylin, S.; Hasegawa, Y.; Shinoda, K.; Luijten, I.H.N.; Chang, J.W.; Sharp, L.Z.; Cravatt, B.F.; Saez, E.; Kajimura, S. ThermoMouse: An in vivo model to identify modulators of UCP1 expression in brown adipose tissue. Cell Rep., 2014, 9, 1584-159.
Claycombe, K.J.; Vomhof-DeKrey, E.E.; Roemmich, J.N.; Rhen, T.; Ghribi, O. Maternal low-protein diet causes body weight loss in male, neonate Sprague-Dawley rats involving UCP-1-mediated thermogenesis. J. Nutr. Biochem., 2015, 26, 729-735.
Liu, X.; Pan, S.; Li, X.; Sun, Q.; Yang, X.; Zhao, R. Maternal low-protein diet affects myostatin signaling and protein synthesis in skeletal muscle of offspring piglets at weaning stage. Eur. J. Nutr., 2015, 54, 971-979.
Wang, H.; Wilson, G.J.; Zhou, D.; Lezmi, S.; Chen, X.; Layman, D.K.; Pan, Y.X. Induction of autophagy through the activating transcription factor 4 (ATF4)-dependent amino acid response pathway in maternal skeletal muscle may function as the molecular memory in response to gestational protein restriction to alert offspring to maternal nutrition. Br. J. Nutr., 2015, 114, 519-532.
Rehfeldt, C.; Lefaucheur, L.; Block, J.; Stabenow, B.; Pfuhl, R.; Otten, W.; Metges, C.C.; Kalbe, C. Limited and excess protein intake of pregnant gilts differently affects body composition and cellularity of skeletal muscle and subcutaneous adipose tissue of newborn and weanling piglets. Eur. J. Nutr., 2012, 51, 151-165.
Nie, C.; He, T.; Zhang, W.; Zhang, G.; Ma, X. Branched chain amino acids: Beyond nutrition metabolism. Int. J. Mol. Sci., 2018, 19, 954.
Brown, L.D.; Green, A.S.; Limesand, S.W.; Rozance, P.J. Maternal amino acid supplementation for intrauterine growth restriction. Front. Biosci. (Schol. Ed.), 2011, 3, 428-444.
Ji, Y.; Wu, Z.; Dai, Z.; Sun, K.; Wang, J.; Wu, G. Nutritional epigenetics with a focus on amino acids: implications for the development and treatment of metabolic syndrome. J. Nutr. Biochem., 2016, 27, 1-8.
Williams, S.R.; Yang, Q.; Chen, F.; Liu, X.; Keene, K.L.; Jacques, P.; Chen, W.M.; Weinstein, G.; Hsu, F.C.; Beiser, A.; Wang, L.; Bookman, E.; Doheny, K.F.; Wolf, P.A.; Zilka, M.; Selhub, J.; Nelson, S.; Gogarten, S.M.; Worrall, B.B.; Seshadri, S.; Sale, M.M. Genomics and randomized trials network; Framingham Heart Study. Genome-wide meta-analysis of homocysteine and methionine metabolism identifies five one carbon metabolism loci and a novel association of ALDH1L1 with ischemic stroke. PLoS Genet., 2014, 10e1004214
Chandler, T.L.; White, H.M. Choline and methionine differentially alter methyl carbon metabolism in bovine neonatal hepatocytes. PLoS One, 2017, 12e0171080
Kalhan, S.C. One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health. Mol. Cell. Endocrinol., 2016, 435, 48-60.
Fontagné-Dicharry, S.; Alami-Durante, H.; Arag, O.C.; Kaushik, S.J.; Geurden, I. Parental and early-feeding effects of dietary methionine in rainbow trout (Oncorhynchus mykiss). Aquaculture, 2017, 469, 16-27.
Aissa, A.F.; Tryndyak, V.; De Conti, A.; Melnyk, S.; Gomes, T.D.; Bianchi, M.L. Effect of methionine deficient and methionine supplemented diets on the hepatic one carbon and lipid metabolism in mice. Mol. Nutr. Food Res., 2014, 58, 1502-1512.
Mattocks, D.A.; Mentch, S.J.; Shneyder, J.; Ables, G.P.; Sun, D.; Richie, J.P., Jr; Locasale, J.W.; Nichenametla, S.N. Short term methionine restriction increases hepatic global DNA methylation in adult but not young male C57BL/6J mice. Exp. Gerontol., 2017, 88, 1-8.
Wang, L.; Chen, L.; Tan, Y.; Wei, J.; Chang, Y.; Jin, T. Betaine supplement alleviates hepatic triglyceride accumulation of apolipoprotein E deficient mice via reducing methylation of peroxisomal proliferator-activated receptor alpha promoter. Lipids Health Dis., 2013, 12, 1390.
Maddocks, O.D.; Labuschagne, C.F.; Adams, P.D.; Vousden, K.H. Serine metabolism supports the methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells. Mol. Cell, 2016, 61, 210-221.
Gregory, J.F.; Cuskelly, G.J.; Shane, B.; Toth, J.P.; Baumgartner, T.G.; Stacpoole, P.W. Primed, constant infusion with [2H3]serine allows in vivo kinetic measurement of serine turnover, homocysteine remethylation, and transsulfuration processes in human one-carbon metabolism. Am. J. Clin. Nutr., 2000, 72, 1535-1541.
He, T.; He, L.; Gao, E.; Hu, J.; Zang, J.; Wang, C.; Zhao, J.; Ma, X. Fat deposition deficiency is critical for the high mortality of pre-weanling newborn piglets. J. Anim. Sci. Biotechnol., 2018, 9, 66.
Amin, F.U.; Shah, S.A.; Kim, M.O. Glycine inhibits ethanol-induced oxidative stress, neuroinflammation and apoptotic neurodegeneration in postnatal rat brain. Neurochem. Int., 2016, 96, 1-12.
Yue, J.T.; Mighiu, P.I.; Naples, M.; Adeli, K.; Lam, T.K. Glycine normalizes hepatic triglyceride-rich VLDL secretion by triggering the CNS in high-fat fed rats. Circ. Res., 2012, 110, 1345-1354.
Shyh-Chang, N.; Locasale, J.W.; Lyssiotis, C.A.; Zheng, Y.; Teo, R.Y.; Ratanasirintrawoot, S.; Zhang, J.; Onder, T.; Unternaehrer, J.J.; Zhu, H.; Asara, J.M.; Daley, G.Q.; Cantley, L.C. Influence of threonine metabolism on S-adenosylmethionine and histone methylation. Science, 2013, 339, 222-226.
Teodoro, G.F.; Vianna, D.; Torres-Leal, F.L.; Pantaleão, L.C.; Matos-Neto, E.M.; Donato, J., Jr; Tirapegui, J. Leucine is essential for attenuating fetal growth restriction caused by a protein-restricted diet in rats. J. Nutr., 2012, 142, 924-930.
Goberdhan, D.C.; Wilson, C.; Harris, A.L. Amino Acid sensing by mTORC1: Intracellular transporters mark the spot. Cell Metab., 2016, 23, 580-589.
Anthony, J.C.; Yoshizawa, F.; Anthony, T.G.; Vary, T.C.; Jefferson, L.S.; Kimball, S.R. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J. Nutr., 2000, 130, 2413-2419.

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