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Gestational Protein Restriction in Wistar Rats; Effect of Taurine Supplementation on Properties of Newborn Skeletal Muscle

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Taurine 10

Abstract

Taurine ameliorates changes occurring in newborn skeletal muscle as a result of gestational protein restriction in C57BL/6 mice, but taurine supplementation effects may be exaggerated in C57BL/6 mice due to their inherent excessive taurinuria.

We examined if maternal taurine supplementation could ameliorate changes in gene expression levels, properties of mitochondria, myogenesis, and nutrient transport and sensing, in male newborn skeletal muscle caused by a maternal low protein (LP) diet in Wistar rats.

LP diet resulted in an 11% non-significant decrease in birth weight, which was not rescued by taurine supplementation (LP-Tau). LP-Tau offspring had significantly lower birth weight compared to controls. Gene expression profiling revealed 895 significantly changed genes, mainly an LP-induced down-regulation of genes involved in protein translation. Taurine fully or partially rescued 32% of these changes, but with no distinct pattern as to which genes were rescued.

Skeletal muscle taurine content in LP-Tau offspring was increased, but no changes in mRNA levels of the taurine synthesis pathway were observed. Taurine transporter mRNA levels, but not protein levels, were increased by LP diet.

Nutrient sensing signaling pathways were largely unaffected in LP or LP-Tau groups, although taurine supplementation caused a decrease in total Akt and AMPK protein levels. PAT4 amino acid transporter mRNA was increased by LP, and normalized by taurine supplementation.

In conclusion, gestational protein restriction in rats decreased genes involved in protein translation in newborn skeletal muscle and led to changes in nutrient transporters. Taurine partly rescued these changes, hence underscoring the importance of taurine in development.

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Abbreviations

ACTB:

Beta-actin

ADO:

Cysteamine dioxygenase

ATF4:

Activating transcription factor 4

CDO:

Cysteine dioxygenase

CK:

Creatine kinase

CON:

Control

CS:

Citrate synthase

CSAD:

Cysteinesulfinic acid decarboxylase

GAPDH:

Glyceraldehyde-3-Phosphate Dehydrogenase

gDNA:

Genomic DNA

GLUT:

Glucose transporter

IUGR:

Intrauterine growth restriction

LP:

Low protein

LP-TAU:

Low protein diet with taurine supplementation

MEF:

Myocyte enhancer factor

MHC:

Myosin heavy chain

mtDNA:

Mitochondrial DNA

Myf5:

Myogenic factor 5

Myo:

Myosin

MyoD:

Myogenic differentiation 1

Ndufb6:

NADH Dehydrogenase (Ubiquinone) 1 beta subcomplex 6

Ndufs1:

NADH Dehydrogenase (Ubiquinone) Fe–S Protein 1

PDK1:

Phosphoenolpyruvate carboxykinase 1

PDK4:

Pyruvate dehydrogenase kinase 4

PGC-1α:

Peroxisome proliferator-activated receptor γ, coactivator-1α

PGC-1β:

Peroxisome proliferator-activated receptor γ, coactivator-1β

PPARα:

Peroxisome proliferator activated receptor α

PPARγ:

Peroxisome proliferator activated receptor γ

REDD1:

DNA-Damage-Inducible Transcript 4 (DDIT4)

S6K1:

Ribosomal Protein S6 Kinase

TauT:

Taurine transporter

TFAM:

Transcriptional factor A, mitochondrial

References

  • Abdul-Ghani MA, DeFronzo RA (2010) Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol 2010:476279. doi:10.1155/2010/476279

    Article  PubMed  PubMed Central  Google Scholar 

  • Armitage JA, Khan IY, Taylor PD et al (2004) Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol Lond 561:355–377. doi:10.1113/jphysiol.2004.072009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bagley PJ, Stipanuk MH (1994) The activities of rat hepatic cysteine dioxygenase and cysteinesulfinate decarboxylase are regulated in a reciprocal manner in response to dietary casein level. J Nutr 124:2410–2421

    CAS  PubMed  Google Scholar 

  • Bayol S, Jones D, Goldspink G, Stickland NC (2004) The influence of undernutrition during gestation on skeletal muscle cellularity and on the expression of genes that control muscle growth. Br J Nutr 91:331–339. doi:10.1079/BJN20031070

    Article  CAS  PubMed  Google Scholar 

  • Bella DL, Hahn C, Stipanuk MH (1999) Effects of nonsulfur and sulfur amino acids on the regulation of hepatic enzymes of cysteine metabolism. Am J Phys 277:E144–E153

    CAS  Google Scholar 

  • Boujendar S, Reusens B, Merezak S et al (2002) Taurine supplementation to a low protein diet during foetal and early postnatal life restores a normal proliferation and apoptosis of rat pancreatic islets. Diabetologia 45:856–866

    Article  CAS  PubMed  Google Scholar 

  • Boujendar S, Arany E, Hill D et al (2003) Taurine supplementation of a low protein diet fed to rat dams normalizes the vascularization of the fetal endocrine pancreas. J Nutr 133:2820–2825

    CAS  PubMed  Google Scholar 

  • Cetin I, Corbetta C, Sereni LP et al (1990) Umbilical amino acid concentrations in normal and growth-retarded fetuses sampled in utero by cordocentesis. Am J Obstet Gynecol 162:253–261

    Article  CAS  PubMed  Google Scholar 

  • Chesney RW, Scriver CR, Mohyuddin F (1976) Localization of the membrane defect in transepithelial transport of taurine by parallel studies in vivo and in vitro in hypertaurinuric mice. J Clin Invest 57:183–193. doi:10.1172/JCI108258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Costello PM, Rowlerson A, Astaman NA et al (2008) Peri-implantation and late gestation maternal undernutrition differentially affect fetal sheep skeletal muscle development. J Physiol Lond 586:2371–2379. doi:10.1113/jphysiol.2008.150987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dwyer CM, Stickland NC (1992) Does the anatomical location of a muscle affect the influence of undernutrition on muscle fibre number? J Anat 181(Pt 2):373–376

    PubMed  PubMed Central  Google Scholar 

  • Dwyer CM, Madgwick AJ, Ward SS, Stickland NC (1995) Effect of maternal undernutrition in early gestation on the development of fetal myofibres in the guinea-pig. Reprod Fertil Dev 7:1285–1292

    Article  CAS  PubMed  Google Scholar 

  • Economides DL, Nicolaides KH, Gahl WA et al (1989) Plasma amino acids in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol 161:1219–1227

    Article  CAS  PubMed  Google Scholar 

  • Gam CMBF, Mortensen OH, Qvortrup K et al (2014) Effect of high-fat diet on rat myometrium during pregnancy-isolated myometrial mitochondria are not affected. Pflugers Arch. doi:10.1007/s00424-014-1599-7

    PubMed  Google Scholar 

  • Greenwood PL, Slepetis RM, Hermanson JW, Bell AW (1999) Intrauterine growth retardation is associated with reduced cell cycle activity, but not myofibre number, in ovine fetal muscle. Reprod Fertil Dev 11:281–291

    Article  CAS  PubMed  Google Scholar 

  • Hales CN, Barker DJ (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35:595–601

    Article  CAS  PubMed  Google Scholar 

  • Harris H, Searle AG (1953) Urinary amino-acids in mice of different genotypes. Ann Eugenics 17:165–167

    Article  CAS  Google Scholar 

  • Heller-Stilb B, van Roeyen C, Rascher K et al (2002) Disruption of the taurine transporter gene (taut) leads to retinal degeneration in mice. FASEB J 16:231–233. doi:10.1096/fj.01-0691fje

    CAS  PubMed  Google Scholar 

  • Huang DW, Sherman BT, Zheng X et al (2009) Extracting biological meaning from large gene lists with DAVID. Curr Protoc Bioinformatics Chapter 13:Unit 13.11. doi:10.1002/0471250953.bi1311s27

    Google Scholar 

  • Ito T, Kimura Y, Uozumi Y et al (2008) Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy. J Mol Cell Cardiol 44:927–937. doi:10.1016/j.yjmcc.2008.03.001

    Article  CAS  PubMed  Google Scholar 

  • Ito T, Yoshikawa N, Inui T et al (2014a) Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice. PLoS One 9:e107409. doi:10.1371/journal.pone.0107409

    Article  PubMed  PubMed Central  Google Scholar 

  • Ito T, Yoshikawa N, Schaffer SW, Azuma J (2014b) Tissue taurine depletion alters metabolic response to exercise and reduces running capacity in mice. J Amino Acids 2014:964680. doi:10.1155/2014/964680

    Article  PubMed  PubMed Central  Google Scholar 

  • Lambert IH, Kristensen DM, Holm JB, Mortensen OH (2015) Physiological role of taurine—from organism to organelle. Acta Physiol (Oxford) 213:191–212. doi:10.1111/apha.12365

    Article  CAS  Google Scholar 

  • Larsen S, Nielsen J, Hansen CN et al (2012) Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J Physiol Lond 590:3349–3360. doi:10.1113/jphysiol.2012.230185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larsen LH, Ørstrup LKH, Hansen SH et al (2013) The effect of long-term taurine supplementation and fructose feeding on glucose and lipid homeostasis in Wistar rats. Adv Exp Med Biol 776:39–50. doi:10.1007/978-1-4614-6093-0_5

    Article  CAS  PubMed  Google Scholar 

  • Larsen LH, Ørstrup LKH, Hansen SH et al (2015) Fructose feeding changes taurine homeostasis in wistar rats. Adv Exp Med Biol 803:695–706. doi:10.1007/978-3-319-15126-7_55

    Article  PubMed  Google Scholar 

  • Li M, Reynolds CM, Sloboda DM et al (2013) Effects of taurine supplementation on hepatic markers of inflammation and lipid metabolism in mothers and offspring in the setting of maternal obesity. PLoS One 8:e76961. doi:10.1371/journal.pone.0076961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li M, Reynolds CM, Sloboda DM et al (2015) Maternal taurine supplementation attenuates maternal fructose-induced metabolic and inflammatory dysregulation and partially reverses adverse metabolic programming in offspring. J Nutr Biochem 26:267–276. doi:10.1016/j.jnutbio.2014.10.015

    Article  PubMed  Google Scholar 

  • Merezak S, Reusens B, Renard A et al (2004) Effect of maternal low-protein diet and taurine on the vulnerability of adult Wistar rat islets to cytokines. Diabetologia 47:669–675

    Article  CAS  PubMed  Google Scholar 

  • Mortensen OH, Frandsen L, Schjerling P et al (2006) PGC-1alpha and PGC-1beta have both similar and distinct effects on myofiber switching toward an oxidative phenotype. Am J Physiol Endocrinol Metab 291:E807–E816

    Article  CAS  PubMed  Google Scholar 

  • Mortensen OH, Olsen HL, Frandsen L et al (2010a) Gestational protein restriction in mice has pronounced effects on gene expression in newborn offspring’s liver and skeletal muscle; protective effect of taurine. Pediatr Res 67:47–53. doi:10.1203/PDR.0b013e3181c4735c

    Article  CAS  PubMed  Google Scholar 

  • Mortensen OH, Olsen HL, Frandsen L et al (2010b) A maternal low protein diet has pronounced effects on mitochondrial gene expression in offspring liver and skeletal muscle; protective effect of taurine. J Biomed Sci 17(Suppl 1):S38. doi:10.1186/1423-0127-17-S1-S38

    Article  PubMed  PubMed Central  Google Scholar 

  • Mortensen OH, Larsen LH, Ørstrup LKH et al (2014) Developmental programming by high fructose decreases phosphorylation efficiency in aging offspring brain mitochondria, correlating with enhanced UCP5 expression. J Cereb Blood Flow Metab 34:1205–1211. doi:10.1038/jcbfm.2014.72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Osgerby JC, Wathes DC, Howard D, Gadd TS (2002) The effect of maternal undernutrition on ovine fetal growth. J Endocrinol 173:131–141

    Article  CAS  PubMed  Google Scholar 

  • Ozanne SE, Smith GD, Tikerpae J, Hales CN (1996) Altered regulation of hepatic glucose output in the male offspring of protein-malnourished rat dams. Am J Phys 270:E559–E564

    CAS  Google Scholar 

  • Ozanne SE, Jensen CB, Tingey KJ et al (2005) Low birthweight is associated with specific changes in muscle insulin-signalling protein expression. Diabetologia 48:547–552. doi:10.1007/s00125-005-1669-7

    Article  CAS  PubMed  Google Scholar 

  • Park HK, Jin CJ, Cho YM et al (2004) Changes of mitochondrial DNA content in the male offspring of protein-malnourished rats. Ann N Y Acad Sci 1011:205–216

    Article  CAS  PubMed  Google Scholar 

  • Petrik J, Reusens B, Arany E et al (1999) A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II. Endocrinology 140:4861–4873. doi:10.1210/endo.140.10.7042

    Article  CAS  PubMed  Google Scholar 

  • Poulsen P, Vaag AA, Kyvik KO et al (1997) Low birth weight is associated with NIDDM in discordant monozygotic and dizygotic twin pairs. Diabetologia 40:439–446

    Article  CAS  PubMed  Google Scholar 

  • Prakash YS, Fournier M, Sieck GC (1993) Effects of prenatal undernutrition on developing rat diaphragm. J Appl Physiol 75:1044–1052

    CAS  PubMed  Google Scholar 

  • Reusens B, Dahri S, Snoech A et al (1995) Long-term consequences of diabetes and its complications may have a fetal origin: experimental and epidemiological evidence. Nestle Nutr Workshop Ser 35:187–198

    Google Scholar 

  • Reusens B, Sparre T, Kalbe L et al (2008) The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation. Diabetologia 51:836–845. doi:10.1007/s00125-008-0956-5

    Article  CAS  PubMed  Google Scholar 

  • Snoeck A, Remacle C, Reusens B, Hoet JJ (1990) Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biol Neonate 57:107–118

    Article  CAS  PubMed  Google Scholar 

  • Stipanuk MH, Ueki I, Dominy JE et al (2009) Cysteine dioxygenase: a robust system for regulation of cellular cysteine levels. Amino Acids 37:55–63. doi:10.1007/s00726-008-0202-y

    Article  CAS  PubMed  Google Scholar 

  • Sturman JA (1993) Taurine in development. Physiol Rev 73:119–147

    CAS  PubMed  Google Scholar 

  • Suzuki T, Suzuki T, Wada T et al (2002) Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases. EMBO J 21:6581–6589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsuboyama-Kasaoka N, Shozawa C, Sano K et al (2006) Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity. Endocrinology 147:3276–3284. doi:10.1210/en.2005-1007

    Article  CAS  PubMed  Google Scholar 

  • Warskulat U, Flögel U, Jacoby C et al (2004) Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised. FASEB J 18:577–579. doi:10.1096/fj.03-0496fje

    CAS  PubMed  Google Scholar 

  • Whishaw IQ, Kolb B (2004) The behavior of the laboratory rat: a handbook with tests. Oxford University Press, Oxford

    Book  Google Scholar 

  • Wilson SJ, Ross JJ, Harris AJ (1988) A critical period for formation of secondary myotubes defined by prenatal undernourishment in rats. Development 102:815–821

    CAS  PubMed  Google Scholar 

  • Wu G, Pond WG, Ott T, Bazer FW (1998) Maternal dietary protein deficiency decreases amino acid concentrations in fetal plasma and allantoic fluid of pigs. J Nutr 128:894–902

    CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Mrs. Bettina Starup Mentz and Mrs. Lis Frandsen, Section for Cellular and Metabolic Research, Dept. of Biomedical Sciences, University of Copenhagen, for expert technical assistance during the conductance of the experiments. This research was supported by Novo Nordisk Fonden, and The Danish Medical Research Council grant #271-07-0732.

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Correspondence to Ole Hartvig Mortensen .

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Larsen, L.H., Sandø-Pedersen, S., Ørstrup, L.K.H., Grunnet, N., Quistorff, B., Mortensen, O.H. (2017). Gestational Protein Restriction in Wistar Rats; Effect of Taurine Supplementation on Properties of Newborn Skeletal Muscle. In: Lee, DH., Schaffer, S.W., Park, E., Kim, H.W. (eds) Taurine 10. Advances in Experimental Medicine and Biology, vol 975. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1079-2_34

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