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Transcriptomic and metabolomic responses induced in the livers of growing pigs by a short-term intravenous infusion of sodium butyrate

Published online by Cambridge University Press:  20 February 2018

E. Ren
Affiliation:
Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing210095, Jiangsu, China
X. Chen
Affiliation:
Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing210095, Jiangsu, China
S. Yu
Affiliation:
Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing210095, Jiangsu, China
J. Xu
Affiliation:
Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing210095, Jiangsu, China
Y. Su*
Affiliation:
Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing210095, Jiangsu, China
W. Zhu
Affiliation:
Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing210095, Jiangsu, China
*
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Abstract

Previous studies showed that butyrate played benefit roles in the health and metabolism of animals. However, little information on the effects of butyrate on the metabolism of piglets at the extraintestinal level is available. The present study investigated transcriptomic and metabolomic responses in the livers of pigs to evaluate the effects of intravenous sodium butyrate (SB) on the body’s metabolism at the extraintestinal level. A total of 12 Duroc×Landrace×Large White growing barrows (60 days of age) fitted with jugular vein cannula were randomly allocated to either the SB group or the control (CO) group. Pigs in the SB group were intravenously infused with 10 ml SB (200 mmol/l) for 7 days, whereas pigs in the CO group were treated with the same amount of saline. The livers of pigs were collected for gene expression and metabolome analyses. The RNA sequencing (RNA-Seq) analysis showed that the mRNA expression of Acyl-CoA synthetase long-chain family member 1 (ACSL1), carnitine palmitoyltransferase 1A (CPT1A), acetyl-CoA acyltransferase 2 (ACAA2) and phosphoenolpyruvate carboxykinase 1 (PCK1) were downregulated (Q<0.05), whereas fatty acid binding protein 1 (FABP1) and cytochrome P450 family 7 subfamily A member 1 (CYP7A1) were upregulated (P<0.05) by SB treatment, indicating a decrease in fatty acid oxidation and gluconeogenesis and an increase in fatty acid transportation and cholesterol metabolism. Gas chromatography-mass spectrometry analysis showed that raffinose was enriched in the SB group compared with the CO group, indicating a decrease in metabolism of galactose. Moreover, SB treatment significantly decreased the concentration of blood cholesterol. The results suggest that a short-term intravenous infusion of SB could modulate hepatic lipid metabolism by decreasing fatty acid oxidation and increasing fatty acid transportation and cholesterol metabolism.

Type
Research Article
Copyright
© The Animal Consortium 2018 

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References

Abe, Y, Okada, T, Kuromori, Y, Hara, M, Saito, E, Iwata, F, Harada, K and Mugishima, H 2009. Apolipoprotein A-V is a potent modulator of HDL and VLDL components in preadolescent children. Journal of Atherosclerosis and Thrombosis 16, 121126.Google Scholar
Anderson, JW and Bridges, SR 1984. Short-chain fatty acid fermentation products of plant fiber affect glucose metabolism of isolated rat hepatocytes. Experimental Biology and Medicine 177, 372376.Google Scholar
Astbury, SM and Corfe, BM 2012. Uptake and metabolism of the short-chain fatty acid butyrate, a critical review of the literature. Current Drug Metabolism 13, 815821.Google Scholar
Benjamini, Y and Hochberg, Y 1995. Controlling the false discovery rate – a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series B-Methodological 57, 289300.Google Scholar
Bongiorni, S, Gruber, C, Chillemi, G, Bueno, S, Failla, S, Moioli, B, Ferrè, F and Valentini, A 2016. Skeletal muscle transcriptional profiles in two Italian beef breeds, Chianina and Maremmana, reveal breed specific variation. Molecular Biology Reports 43, 253268.Google Scholar
Borghini, I, James, RW, Blatter, MC and Pometta, D 1991. Distribution of apolipoprotein E between free and A-II complexed forms in very-low- and high-density lipoproteins: functional implications. Biochimica Et Biophysica Acta 1083, 139146.Google Scholar
Brown, AJ, Goldsworthy, SM, Barnes, AA, Eilert, MM, Tcheang, L, Daniels, D, Muir, AI, Wigglesworth, MJ, Kinghorn, I, Fraser, NJ, Pike, NB, Strum, JC, Steplewski, KM, Murdock, PR, Holder, JC, Marshall, FH, Szekeres, PG, Wilson, S, Ignar, DM, Foord, SM, Wise, A and Dowell, SJ 2003. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. Journal of Biological Chemistry 278, 1131211319.Google Scholar
Davie, JR 2003. Inhibition of histone deacetylase activity by butyrate. Journal of Nutrition 133 (suppl. 7), 24852493.Google Scholar
Ditullio, NW, Berkoff, CE, Blank, B, Kostos, V, Stack, EJ and Saunders, HL 1974. 3-mercaptopicolinic acid, an inhibitor of gluconeogenesis. Biochemical Journal 138, 387394.Google Scholar
Eriksson, L, Trygg, J and Wold, S 2008. CV-ANOVA for significance testing of PLS and OPLS®; models. Journal of Chemometrics 22, 594600.Google Scholar
Gallis, JL, Tissier, P, Gin, H and Beauvieux, MC 2007. Decrease in oxidative phosphorylation yield in presence of butyrate in perfused liver isolated from fed rats. BMC Physiology 7, 110.Google Scholar
Hall, AM, Smith, AJ and Bernlohr, DA 2003. Characterization of the acyl-CoA synthetase activity of purified murine fatty acid transport protein 1. Journal of Biological Chemistry 278, 4300843013.Google Scholar
Hubacek, JA and Bobkova, DD 2006. Role of cholesterol 7α-hydroxylase (CYP7A1) in nutrigenetics and pharmacogenetics of cholesterol lowering. Molecular Diagnosis and Therapy 10, 93100.Google Scholar
Kantor, PF, Lucien, A, Kozak, R and Lopaschuk, GD 2000. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circulation Research. 86, 580588.Google Scholar
Kerner, J and Hoppel, C 2000. Fatty acid import into mitochondria. Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids 1486, 117.Google Scholar
Lackey, DE, Lynch, CJ, Olson, KC, Mostaedi, R, Ali, M, Smith, WH, Karpe, F, Humphreys, S, Bedinger, DH and Dunn, TN 2013. Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity. American Journal of Physiology – Endocrinology and Metabolism 304, e1175.Google Scholar
Lagrost, L, Gambert, P, Boquillon, M and Lallemant, C 1989. Evidence for high density lipoproteins as the major apolipoprotein A-IV-containing fraction in normal human serum. Journal of Lipid Research 30, 15251534.Google Scholar
Martin, GG, Danneberg, H, Kumar, LS, Atshaves, BP, Erol, E, Bader, M, Schroeder, F and Binas, B 2003. Decreased liver fatty acid binding capacity and altered liver lipid distribution in mice lacking the liver fatty acid-binding protein gene. Journal of Biological Chemistry 278, 2142921438.Google Scholar
Mashek, DG, Li, LO and Coleman, RA 2006. Rat long-chain acyl-CoA synthetase mRNA, protein, and activity vary in tissue distribution and in response to diet. Journal of Lipid Research 47, 20042010.Google Scholar
Mortazavi, A, Williams, BA, Mccue, K, Schaeffer, L and Wold, B 2008. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nature Methods 5, 621628.Google Scholar
Nicholson, JK, Holmes, E, Kinross, J, Burcelin, R, Gibson, G, Jia, W and Pettersson, S 2012. Host-gut microbiota metabolic interactions. Science 336, 12621267.Google Scholar
Nookaew, I, Papini, M, Pornputtapong, N, Scalcinati, G, Fagerberg, L, Uhlén, M and Nielsen, J 2012. A comprehensive comparison of RNA-Seq-based transcriptome analysis from reads to differential gene expression and cross-comparison with microarrays: a case study in Saccharomyces cerevisiae . Nucleic Acids Research 40, 1008410097.Google Scholar
Oczkowicz, M, Świątkiewicz, M, Ropkamolik, K, Gurgul, A and Żukowski, K 2016. Effects of different sources of fat in the diet of pigs on the liver transcriptome estimated by RNA-seq. Annals of Animal Science 16, 10731090.Google Scholar
Park, SK, Jeong, JY, Cho, ES, Jeong, YD and Park, CS 2017. RNA-Seq reveals differentially expressed genes of pig vaccinated with modified live attenuated porcine epidemic diarrhea. Pakistan Journal of Zoology 49, 11071107.Google Scholar
Rapaport, F, Khanin, R, Liang, Y, Pirun, M, Krek, A, Zumbo, P, Mason, CE, Socci, ND and Betel, D 2013. Comprehensive evaluation of differential gene expression analysis methods for RNA-seq data. Genome Biology 14, R95.Google Scholar
Rémésy, C and Demigné, C 1983. Changes in availability of glucogenic and ketogenic substrates and liver metabolism in fed or starved rats. Annals of Nutrition and Metabolism 27, 5770.Google Scholar
Robinson, MD, McCarthy, DJ and Smyth, GK 2010. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139140.Google Scholar
Schroeder, F, Petrescu, AD, Huang, H, Atshaves, BP, McIntosh, AL, Martin, GG, Hostetler, HA, Vespa, A, Landrock, D, Landrock, KK, Payne, HR and Kier, AB 2008. Role of fatty acid binding proteins and long chain fatty acids in modulating nuclear receptors and gene transcription. Lipids 43, 117.Google Scholar
Sun, J, Xie, M, Huang, Z, Li, H, Sun, R, Wang, J, Xi, Q, Wu, T and Zhang, Y 2017. Integrated analysis of non-coding RNA and mRNA expression profiles of 2 pig breeds differing in muscle traits. Journal of Animal Science 95, 10921103.Google Scholar
Sun, Y, Yu, K, Zhou, L, Fang, L, Su, Y and Zhu, W 2016. Metabolomic and transcriptomic responses induced in the livers of pigs by the long-term intake of resistant starch. Journal of Animal Science 94, 10831094.Google Scholar
Trapnell, C, Pachter, L and Salzberg, SL 2009. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 11051111.Google Scholar
Trapnell, C, Williams, BA, Pertea, G, Mortazavi, A, Kwan, G, van Baren, MJ, Salzberg, SL, Wold, BJ and Pachter, L 2010. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nature Biotechnology 28, 511515.Google Scholar
Valera, A, Pujol, A, Pelegrin, M and Bosch, F 1994. Transgenic mice overexpressing phosphoenolpyruvate carboxykinase develop non-insulin-dependent diabetes mellitus. Proceedings of the National Academy of Sciences of the United States of America 91, 91519154.Google Scholar
Wang, YL, Lawler, D, Larson, B, Ramadan, Z, Kochhar, S, Holmes, E and Nicholson, JK 2007. Metabonomic investigations of aging and caloric restriction in a life-long dog study. Journal of Proteome Research 6, 18461854.Google Scholar
Wang, Z, Gerstein, M and Snyder, M 2009. RNA-Seq: a revolutionary tool for transcriptomics. Nature Reviews Genetics 10, 5763.Google Scholar
Wiese, TJ, Lambeth, DO and Ray, PD 1991. The intracellular distribution and activities of phosphoenolpyruvate carboxykinase isozymes in various tissues of several mammals and birds. Comparative Biochemistry and Physiology Part B Comparative Biochemistry 100, 297302.Google Scholar
Xia, JG, Psychogios, N, Young, N and Wishart, DS 2009. MetaboAnalyst: a web server for metabolomic data analysis and interpretation. Nucleic Acids Research, https://doi.org/10.1093/nar/gkp356, Published online by Oxford University Press 8 May 2009.Google Scholar
Xie, WD, Wang, H, Zhang, JF, Li, JN, Can, Y, Qing, L, Kung, HF and Zhang, YO 2011. Enhanced peroxisomal β-oxidation metabolism in visceral adipose tissues of high-fat diet-fed obesity-resistant C57BL/6 mice. Experimental and Therapeutic Medicine 2, 309315.Google Scholar
Yang, JL, Lee, HJ and Kim, YH 2005. Effect of hormones and short chain fatty acids on CYP7A1 gene expression in HepG2 cell. Journal of the Korean Society of Food Science & Nutrition 34, 573580.Google Scholar
Yu, S, Ren, E, Xu, J, Su, Y and Zhu, W 2016. Effects of early intervention with sodium butyrate on lipid metabolism-related gene expression and liver metabolite profiles in neonatal piglets. Livestock Science 195, 8086.Google Scholar
Zhang, L, Du, J, Yano, N, Wang, H, Zhao, YT, Dubielecka, PM, Zhuang, S, Chin, YE, Qin, G and Zhao, TC 2017. Sodium butyrate protects against high fat diet-induced cardiac dysfunction and metabolic disorders in type II diabetic mice. Journal of Cellular Biochemistry 118, 23952408.Google Scholar
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