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Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2

Published online by Cambridge University Press:  20 April 2016

J. Liu ,
Z. Liu ,
L. Gao ,
L. Chen  and
H. Zhang
J. Liu
Affiliation:
State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, People’s Republic of China School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang 621010, Sichuan, People’s Republic of China
Z. Liu
Affiliation:
State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, People’s Republic of China
L. Gao
Affiliation:
State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, People’s Republic of China
L. Chen
Affiliation:
State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, People’s Republic of China
H. Zhang*
Affiliation:
State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, People’s Republic of China
*
†E-mail: zhanghongfu@caas.cn
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Abstract

The objective of the present study was to investigate the intestinal development of newborn intrauterine growth-restricted (IUGR) piglets subjected to normal nutrient intake (NNI) or restricted nutrient intake (RNI). Newborn normal birth weight (NBW) and IUGR piglets were allotted to NNI or RNI levels for 4 weeks from day 8 postnatal. IUGR piglets receiving NNI had similar growth performance compared with that of NBW piglets. Small intestine length and villous height were greater in IUGR piglets fed the NNI than that of piglets fed the RNI. Lactase activity was increased in piglets fed the NNI compared with piglets fed the RNI. Absorptive function, represented by active glucose transport by the Ussing chamber method and messenger RNA (mRNA) expressions of two main intestinal glucose transporters, Na+-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), were greater in IUGR piglets fed the NNI compared with piglets fed the RNI regimen. The apoptotic process, characterized by caspase-3 activity (a sign of activated apoptotic cells) and mRNA expressions of p53 (pro-apoptotic), bcl-2-like protein 4 (Bax) (pro-apoptotic) and B-cell lymphoma-2 (Bcl-2) (anti-apoptotic), were improved in IUGR piglets fed the NNI regimen. To test the hypothesis that improvements in intestinal development of IUGR piglets fed NNI might be mediated through circulating glucagon-like peptide-2 (GLP-2), GLP-2 was injected subcutaneously to IUGR piglets fed the RNI from day 8 to day 15 postnatal. Although the intestinal development of IUGR piglets fed the RNI regimen was suppressed compared with those fed the NNI regimen, an exogenous injection of GLP-2 was able to bring intestinal development to similar levels as NNI-fed IUGR piglets. Collectively, our results demonstrate that IUGR neonates that have NNI levels could improve intestinal function via the regulation of GLP-2.

Keywords

glucagon-like peptide-2intestineintrauterine growth restrictionnutrient intake levelpiglets
Type
Research Article
Information
animal , Volume 10 , Issue 10 , October 2016 , pp. 1645 - 1654
Copyright
© The Animal Consortium 2016 

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References

Andreassen, BU, Paerregaard, A, Schmiegelow, K, Rechnitzer, C, Heilman, C, Hartmann, B, Holst, JJ and Michaelsen, KF 2005. Glucagon-like peptide-2 (GLP-2) response to enteral intake in children during anti-cancer treatment. Journal of Pediatric Gastroenterology and Nutrition 40, 48–53.Google Scholar
Baserga, M, Bertolotto, C, Maclennan, NK, Hsu, JL, Pham, T, Laksana, GS and Lane, RH 2004. Uteroplacental insufficiency decreases small intestine growth and alters apoptotic homeostasis in term intrauterine growth retarded rats. Early Human Development 79, 93–105.Google Scholar
Bateson, P, Barker, D, Clutton-Brock, T, Deb, D, D’Udine, B, Foley, RA, Gluckman, P, Godfrey, K, Kirkwood, T, Lahr, MM, McNamara, J, Metcalfe, NB, Monaghan, P, Spencer, HG and Sultan, SE 2004. Developmental plasticity and human health. Nature 430, 419–421.Google Scholar
Bjornvad, CR, Schmidt, M, Petersen, YM, Jensen, SK, Offenberg, H, Elnif, J and Sangild, PT 2005. Preterm birth makes the immature intestine sensitive to feeding-induced intestinal atrophy. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 289, R1212–R1222.Google Scholar
Brinkman, AS, Murali, SG, Hitt, S, Solverson, PM, Holst, JJ and Ney, DM 2012. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure. American Journal of Physiology. Gastrointestinal and Liver Physiology 303, G610–G622.CrossRefGoogle Scholar
Burrin, DG, Stoll, B, Guan, X, Cui, L, Chang, X and Holst, JJ 2005. Glucagon-like peptide 2 dose-dependently activates intestinal cell survival and proliferation in neonatal piglets. Endocrinology 146, 22–32.Google Scholar
Burrin, DG, Stoll, B, Jiang, R, Chang, X, Hartmann, B, Holst, JJ, Greeley, GH Jr and Reeds, PJ 2000. Minimal enteral nutrient requirements for intestinal growth in neonatal piglets: how much is enough? The American Journal of Clinical Nutrition 71, 1603–1610.Google Scholar
Cummings, MC 1996. Increased p53 mRNA expression in liver and kidney apoptosis. Biochimica et Biophysica Acta 1315, 100–104.Google Scholar
D’Inca, R, Kloareg, M, Gras-Le Guen, C and Le Huërou-Luron, I 2010. Intrauterine growth restriction modifies the developmental pattern of intestinal structure, transcriptomic profile, and bacterial colonization in neonatal pigs. Journal of Nutrition 140, 925–931.Google Scholar
Dodge, ME, Bertolo, RF and Brunton, JA 2012. Enteral feeding induces early intestinal adaptation in a parenterally fed neonatal piglet model of short bowel syndrome. Journal of Parenteral and Enteral Nutrition 36, 205–212.CrossRefGoogle Scholar
Ebner, S, Schoknecht, PA, Reeds, PJ and Burrin, D 1994. Growth and metabolism of gastrointestinal and skeletal muscle tissues in protein-malnourished neonatal pigs. American Journal of Physiology 267, R221–R227.Google Scholar
Edelstone, DI and Holzman, IR 1981. Gastrointestinal tract O2 uptake and regional blood flows during digestion in conscious newborn lambs. American Journal of Physiology 241, G289–G293.Google Scholar
Gabler, NK, Radcliffe, JS, Spencer, JD, Webel, DM and Spurlock, ME 2009. Feeding long-chain n-3 polyunsaturated fatty acids during gestation increases intestinal glucose absorption potentially via the acute activation of AMPK. The Journal of Nutritional Biochemistry 20, 17–25.Google Scholar
Gabler, NK, Spencer, JD, Webel, DM and Spurlock, ME 2007. In utero and postnatal exposure to long chain (n-3) PUFA enhances intestinal glucose absorption and energy stores in weanling pigs. Journal of Nutrition 137, 2351–2358.Google Scholar
Guan, X, Stoll, B, Lu, X, Tappenden, KA, Holst, JJ, Hartmann, B and Burrin, DG 2003. GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets. Gastroenterology 125, 136–147.Google Scholar
Han, F, Hu, L, Xuan, Y, Ding, X, Luo, Y, Bai, S, He, S, Zhang, K and Che, L 2013. Effects of high nutrient intake on the growth performance, intestinal morphology and immune function of neonatal intra-uterine growth-retarded pigs. British Journal of Nutrition 110, 1819–1827.Google Scholar
Hansen, AV, Strathe, AB, Kebreab, E, France, J and Theil, PK 2012. Predicting milk yield and composition in lactating sows: a Bayesian approach. Journal of Animal Science 90, 2285–2298.CrossRefGoogle ScholarPubMed
Ito, J, Uchida, H, Yokote, T, Ohtake, K and Kobayashi, J 2010. Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat. American Journal of Physiology. Gastrointestinal and Liver Physiology 298, G916–G926.Google Scholar
Labarca, C and Paigen, K 1980. A simple, rapid and sensitive DNA assay procedure. Analytical Biochemistry 102, 344–352.Google Scholar
Liu, J, Chen, D, Yao, Y, Yu, B, Mao, X, He, J, Huang, Z and Zheng, P 2012. Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle. PLoS One 7, e34835.Google Scholar
Liu, J, He, J, Yang, Y, Yu, J, Mao, X, Yu, B and Chen, D 2014a. Effects of intrauterine growth retardation and postnatal high-fat diet on hepatic inflammatory response in pigs. Archives of Animal Nutrition 68, 111–125.Google Scholar
Liu, J, He, J, Yu, J, Mao, X, Zheng, P, Huang, Z, Yu, B and Chen, D 2014b. Birth weight alters the response to postnatal high-fat diet-induced changes in meat quality traits and skeletal muscle proteome of pigs. British Journal of Nutrition 111, 1738–1747.Google Scholar
Miyashita, JC and Reed, JC 1995. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80, 293–299.Google ScholarPubMed
Niinikoski, H, Stoll, B, Guan, X, Kansagra, K, Lambert, BD, Stephens, J, Hartmann, B, Holst, JJ and Burrin, DG 2004. Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal piglets. Journal of Nutrition 134, 1467–1474.CrossRefGoogle ScholarPubMed
Oste, M, Van Haver, E, Thymann, T, Sangild, P, Weyns, A and Van Ginneken, CJ 2010. Formula induces intestinal apoptosis in preterm pigs within a few hours of feeding. Journal of Parenteral and Enteral Nutrition 34, 271–279.Google Scholar
Petersen, YM, Hartmann, B, Holst, JJ, Le Huerou-Luron, I, Bjørnvad, CR and Sangild, PT 2003. Introduction of enteral food increases plasma GLP-2 and decreases GLP-2 receptor mRNA abundance during pig development. Journal of Nutrition 133, 1781–1786.Google Scholar
Pfaffl, MW 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research 29, e45.Google Scholar
Sigalet, DL, de Heuvel, E, Wallace, L, Bulloch, E, Turner, J, Wales, PW, Nation, P, Wizzard, PR, Hartmann, B, Assad, M and Holst, JJ 2014. Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs. Regulatory Peptides 188, 70–80.CrossRefGoogle ScholarPubMed
Stoll, B, Chang, X, Fan, MZ, Reeds, PJ and Burrin, DG 2000. Enteral nutrient intake level determines intestinal protein synthesis and accretion rates in neonatal pigs. American Journal of Physiology. Gastrointestinal and Liver Physiology 279, G288–G294.CrossRefGoogle ScholarPubMed
Thymann, T, Møller, HK, Stoll, B, Støy, AC, Buddington, RK, Bering, SB, Jensen, BB, Olutoye, OO, Siggers, RH, Mølbak, L, Sangild, PT and Burrin, DG 2009. Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs. American Journal of Physiology. Gastrointestinal and Liver Physiology 297, G1115–G1125.Google Scholar
Vegge, A, Thymann, T, Lund, P, Stoll, B, Bering, SB, Hartmann, B, Jelsing, J, Qvist, N, Burrin, DG, Jeppesen, PB, Holst, JJ and Sangild, PT 2013. Glucagon-like peptide-2 induces rapid digestive adaptation following intestinal resection in preterm neonates. American Journal of Physiology. Gastrointestinal and Liver Physiology 305, G277–G285.Google Scholar
Wang, X, Lin, G, Liu, C, Feng, C, Zhou, H, Wang, T, Li, D, Wu, G and Wang, J 2014. Temporal proteomic analysis reveals defects in small-intestinal development of porcine fetuses with intrauterine growth restriction. The Journal of Nutritional Biochemistry 25, 785–795.Google Scholar
Weaver, LT, Austin, S and Cole, TJ 1991. Small intestinal length: a factor essential for gut adaptation. Gut 32, 1321–1323.Google Scholar
Wu, G, Bazer, FW, Wallace, JM and Spencer, TE 2006. Board-invited review: intrauterine growth retardation: implications for the animal sciences. Journal of Animal Science 84, 2316–2337.Google Scholar