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PLOS ONE  2013 

Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity

DOI: 10.1371/journal.pone.0076961

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Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may ameliorate the adverse effects observed in offspring following a maternal obesogenic diet but these effects are dependent upon prior maternal nutritional background.


[1]  Hillemeier MM, Weisman CS, Chuang C, Downs DS, McCall-Hosenfeld J, et al. (2011) Transition to overweight or obesity among women of reproductive age. J Womens Health (Larchmt) 20: 703–710.
[2]  Nodine PM, Hastings-Tolsma M (2012) Maternal obesity: improving pregnancy outcomes. MCN Am J Matern Child Nurs 37: 110–115.
[3]  Metzger BE, Cho NH, Roston SM, Radvany R (1993) Prepregnancy weight and antepartum insulin secretion predict glucose tolerance five years after gestational diabetes mellitus. Diabetes Care 16: 1598–1605.
[4]  Kaaja R, Laivuori H, Laakso M, Tikkanen MJ, Ylikorkala O (1999) Evidence of a state of increased insulin resistance in preeclampsia. Metabolism 48: 892–896.
[5]  Catalano PM (2010) Obesity, insulin resistance, and pregnancy outcome. Reproduction 140: 365–371.
[6]  Tiikkainen M, Tamminen M, Hakkinen AM, Bergholm R, Vehkavaara S, et al. (2002) Liver-fat accumulation and insulin resistance in obese women with previous gestational diabetes. Obes Res 10: 859–867.
[7]  Poston L, Harthoorn LF, Van Der Beek EM (2011) Obesity in pregnancy: implications for the mother and lifelong health of the child. A consensus statement. Pediatr Res 69: 175–180.
[8]  Gluckman PD, Hanson MA, Beedle AS (2007) Early life events and their consequences for later disease: a life history and evolutionary perspective. Am J Hum Biol 19: 1–19.
[9]  Fall CH, Osmond C, Barker DJ, Clark PM, Hales CN, et al. (1995) Fetal and infant growth and cardiovascular risk factors in women. BMJ 310: 428–432.
[10]  Curhan GC, Chertow GM, Willett WC, Spiegelman D, Colditz GA, et al. (1996) Birth weight and adult hypertension and obesity in women. Circulation 94: 1310–1315.
[11]  Samuelsson AM, Matthews PA, Argenton M, Christie MR, McConnell JM, et al. (2008) Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension 51: 383–392.
[12]  Howie GJ, Sloboda DM, Kamal T, Vickers MH (2009) Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol 587: 905–915.
[13]  Anuradha CV, Balakrishnan SD (1999) Taurine attenuates hypertension and improves insulin sensitivity in the fructose-fed rat, an animal model of insulin resistance. Can J Physiol Pharmacol 77: 749–754.
[14]  Haber CA, Lam TK, Yu Z, Gupta N, Goh T, et al. (2003) N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress. Am J Physiol Endocrinol Metab 285: E744–753.
[15]  Ito T, Schaffer SW, Azuma J (2012) The potential usefulness of taurine on diabetes mellitus and its complications. Amino Acids 42: 1529–1539.
[16]  Worden JA, Stipanuk MH (1985) A comparison by species, age and sex of cysteinesulfinate decarboxylase activity and taurine concentration in liver and brain of animals. Comp Biochem Physiol B 82: 233–239.
[17]  Franconi F, Di Leo MA, Bennardini F, Ghirlanda G (2004) Is taurine beneficial in reducing risk factors for diabetes mellitus? Neurochem Res 29: 143–150.
[18]  Carneiro EM, Latorraca MQ, Araujo E, Beltra M, Oliveras MJ, et al. (2009) Taurine supplementation modulates glucose homeostasis and islet function. J Nutr Biochem 20: 503–511.
[19]  Nandhini AT, Thirunavukkarasu V, Anuradha CV (2005) Taurine modifies insulin signaling enzymes in the fructose-fed insulin resistant rats. Diabetes Metab 31: 337–344.
[20]  Cherif H, Reusens B, Ahn MT, Hoet JJ, Remacle C (1998) Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet. J Endocrinol 159: 341–348.
[21]  Boujendar S, Reusens B, Merezak S, Ahn MT, Arany E, 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.
[22]  Merezak S, Reusens B, Renard A, Goosse K, Kalbe L, 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.
[23]  Tang C, Marchand K, Lam L, Lux-Lantos V, Thyssen SM, et al. (2013) Maternal taurine supplementation in rats partially prevents the adverse effects of early-life protein deprivation on beta-cell function and insulin sensitivity. Reproduction 145: 609–620.
[24]  Lin S, Hirai S, Yamaguchi Y, Goto T, Takahashi N, et al.. (2013) Taurine improves obesity-induced inflammatory responses and modulates the unbalanced phenotype of adipose tissue macrophages. Mol Nutr Food Res.
[25]  Ainge H, Thompson C, Ozanne SE, Rooney KB (2011) A systematic review on animal models of maternal high fat feeding and offspring glycaemic control. Int J Obes (Lond) 35: 325–335.
[26]  Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412–419.
[27]  Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402–408.
[28]  Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, et al. (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41: 1313–1321.
[29]  Stoeckman AK, Towle HC (2002) The role of SREBP-1c in nutritional regulation of lipogenic enzyme gene expression. J Biol Chem 277: 27029–27035.
[30]  Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, et al. (2003) Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A 100: 12027–12032.
[31]  Foretz M, Pacot C, Dugail I, Lemarchand P, Guichard C, et al. (1999) ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. Mol Cell Biol 19: 3760–3768.
[32]  Postic C, Girard J (2008) Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 118: 829–838.
[33]  Schoonjans K, Staels B, Auwerx J (1996) The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta 1302: 93–109.
[34]  Steineger HH, Sorensen HN, Tugwood JD, Skrede S, Spydevold O, et al. (1994) Dexamethasone and insulin demonstrate marked and opposite regulation of the steady-state mRNA level of the peroxisomal proliferator-activated receptor (PPAR) in hepatic cells. Hormonal modulation of fatty-acid-induced transcription. Eur J Biochem 225: 967–974.
[35]  Hermanowski-Vosatka A, Gerhold D, Mundt SS, Loving VA, Lu M, et al. (2000) PPARalpha agonists reduce 11beta-hydroxysteroid dehydrogenase type 1 in the liver. Biochem Biophys Res Commun 279: 330–336.
[36]  Kim JK, Fillmore JJ, Chen Y, Yu C, Moore IK, et al. (2001) Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A 98: 7522–7527.
[37]  Goldberg IJ, Eckel RH, Abumrad NA (2009) Regulation of fatty acid uptake into tissues: lipoprotein lipase- and CD36-mediated pathways. J Lipid Res 50 Suppl: S86–90
[38]  Havel PJ (2005) Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev 63: 133–157.
[39]  Ouyang X, Cirillo P, Sautin Y, McCall S, Bruchette JL, et al. (2008) Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 48: 993–999.
[40]  Chen SW, Chen YX, Shi J, Lin Y, Xie WF (2006) The restorative effect of taurine on experimental nonalcoholic steatohepatitis. Dig Dis Sci 51: 2225–2234.
[41]  Chang YY, Chou CH, Chiu CH, Yang KT, Lin YL, et al. (2011) Preventive effects of taurine on development of hepatic steatosis induced by a high-fat/cholesterol dietary habit. J Agric Food Chem 59: 450–457.
[42]  Gentile CL, Nivala AM, Gonzales JC, Pfaffenbach KT, Wang D, et al. (2011) Experimental evidence for therapeutic potential of taurine in the treatment of nonalcoholic fatty liver disease. Am J Physiol Regul Integr Comp Physiol 301: R1710–1722.
[43]  Bataller R, Brenner DA (2005) Liver fibrosis. J Clin Invest 115: 209–218.
[44]  Crespo J, Cayon A, Fernandez-Gil P, Hernandez-Guerra M, Mayorga M, et al. (2001) Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 34: 1158–1163.
[45]  Manco M, Marcellini M, Giannone G, Nobili V (2007) Correlation of serum TNF-alpha levels and histologic liver injury scores in pediatric nonalcoholic fatty liver disease. Am J Clin Pathol 127: 954–960.
[46]  Miura K, Kodama Y, Inokuchi S, Schnabl B, Aoyama T, et al.. (2010) Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice. Gastroenterology 139: 323–334 e327.
[47]  Boden G, She P, Mozzoli M, Cheung P, Gumireddy K, et al. (2005) Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver. Diabetes 54: 3458–3465.
[48]  McArthur MJ, Atshaves BP, Frolov A, Foxworth WD, Kier AB, et al. (1999) Cellular uptake and intracellular trafficking of long chain fatty acids. J Lipid Res 40: 1371–1383.
[49]  Schuller-Levis GB, Park E (2003) Taurine: new implications for an old amino acid. FEMS Microbiol Lett 226: 195–202.
[50]  Ahima RS, Flier JS (2000) Adipose tissue as an endocrine organ. Trends Endocrinol Metab 11: 327–332.
[51]  Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, et al. (2002) Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 105: 804–809.
[52]  Elshorbagy AK, Valdivia-Garcia M, Mattocks DA, Plummer JD, Orentreich DS, et al. (2013) Effect of taurine and N-acetylcysteine on methionine restriction-mediated adiposity resistance. Metabolism 62: 509–517.
[53]  Mikami N, Hosokawa M, Miyashita K (2012) Dietary combination of fish oil and taurine decreases fat accumulation and ameliorates blood glucose levels in type 2 diabetic/obese KK-A(y) mice. J Food Sci 77: H114–120.
[54]  Valladolid-Acebes I, Merino B, Principato A, Fole A, Barbas C, et al. (2012) High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission. Am J Physiol Endocrinol Metab 302: E396–402.
[55]  Olney JW, Ho OL (1970) Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine. Nature 227: 609–611.
[56]  Kowluru RA, Engerman RL, Case GL, Kern TS (2001) Retinal glutamate in diabetes and effect of antioxidants. Neurochem Int 38: 385–390.
[57]  Davalli AM, Perego C, Folli FB (2012) The potential role of glutamate in the current diabetes epidemic. Acta Diabetol 49: 167–183.
[58]  Hermanussen M, Garcia AP, Sunder M, Voigt M, Salazar V, et al. (2006) Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite. Eur J Clin Nutr 60: 25–31.
[59]  Yu T, Zhao Y, Shi W, Ma R, Yu L (1997) Effects of maternal oral administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain. Brain Res 747: 195–206.
[60]  Bannai S (1986) Exchange of cystine and glutamate across plasma membrane of human fibroblasts. J Biol Chem 261: 2256–2263.
[61]  Ientile R, Cangemi F, Di Giorgio RM, Macaione S (1992) Excess of taurine supplementation in rat: effects on GABA-related amino acids in developing nervous tissues. Ital J Biochem 41: 183–194.
[62]  Yu X, Xu Z, Mi M, Xu H, Zhu J, et al. (2008) Dietary taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in streptozotocin-induced Sprague-Dawley rats. Neurochem Res 33: 500–507.
[63]  Vickers MH, Clayton ZE, Yap C, Sloboda DM (2011) Maternal fructose intake during pregnancy and lactation alters placental growth and leads to sex-specific changes in fetal and neonatal endocrine function. Endocrinology 152: 1378–1387.
[64]  Chiappini F, Barrier A, Saffroy R, Domart MC, Dagues N, et al. (2006) Exploration of global gene expression in human liver steatosis by high-density oligonucleotide microarray. Lab Invest 86: 154–165.
[65]  Kamari Y, Shaish A, Vax E, Shemesh S, Kandel-Kfir M, et al. (2011) Lack of interleukin-1alpha or interleukin-1beta inhibits transformation of steatosis to steatohepatitis and liver fibrosis in hypercholesterolemic mice. J Hepatol 55: 1086–1094.
[66]  Petrasek J, Bala S, Csak T, Lippai D, Kodys K, et al. (2012) IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice. J Clin Invest 122: 3476–3489.
[67]  Shivananjappa MM (2012) Muralidhara (2012) Taurine attenuates maternal and embryonic oxidative stress in a streptozotocin-diabetic rat model. Reprod Biomed Online 24: 558–566.
[68]  Vickers MH, Gluckman PD, Coveny AH, Hofman PL, Cutfield WS, et al. (2005) Neonatal leptin treatment reverses developmental programming. Endocrinology 146: 4211–4216.
[69]  Vickers MH, Gluckman PD, Coveny AH, Hofman PL, Cutfield WS, et al. (2008) The effect of neonatal leptin treatment on postnatal weight gain in male rats is dependent on maternal nutritional status during pregnancy. Endocrinology 149: 1906–1913.
[70]  Gray C, Li M, Reynolds CM, Vickers MH (2013) Pre-weaning growth hormone treatment reverses hypertension and endothelial dysfunction in adult male offspring of mothers undernourished during pregnancy. PLoS One 8: e53505.


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