Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene

Springer Science and Business Media LLC - Tập 59 Số 6 - Trang 2497-2506 - 2020
Rihua Cong1, Xiaoli Qu2, Hui Zhang1, Yongling Hu1, Silin Ye1, Demin Cai3,4, Xian Li1, Hao-Yu Liu5
1College of Veterinary Medicine, Northwest A and F University, Yangling, China
2School of Life Sciences, Zhengzhou University, Zhengzhou, China
3College of Animal Science and Technology, Yangzhou University, Yangzhou, China
4Department of Biochemistry and Molecular Medicine, University of California at Davis, Sacramento, USA
5Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden

Tóm tắt

Abstract Purpose The aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring. Methods Fourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n = 7) diet or a high-protein (HP, 150% of SP, n = 7) diet during pregnancy. Offspring (one male and one female per group, n = 14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples were analyzed for Tch, insulin and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Liver samples were analyzed for IGFBP-3 and IGF-I mRNA expression by qRT-PCR and for IGFBP-3, IGF1R and growth hormone receptor (GHR) protein expression by Western blotting. The underlying mechanism of IGFBP-3 regulation was determined by methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). Results High-protein exposure resulted in significantly higher body and liver weights of piglets, and it increased their serum T3 and T4 levels at birth and/or at weaning. Furthermore, the IGFBP-3 protein content in the liver and serum was significantly reduced in the HP-exposed weaning piglets, whereas at the transcriptional level IGFBP-3 mRNA expression was downregulated in the livers of HP group piglets. Finally, DNA hypermethylation and higher enrichment of the histone repressive marks H3K27me3 and H3K9me3 were observed. Conclusions Taken together, these results suggest that a maternal high-protein diet during gestation epigenetically reprograms IGFBP-3 gene expression to modulate the hepatic growth axis in weaning piglets.

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Tài liệu tham khảo

Denley A, Cosgrove LJ, Booker GW, Wallace JC, Forbes BE (2005) Molecular interactions of the IGF system. Cytokine Growth Factor Rev 16(4–5):421–439. https://doi.org/10.1016/j.cytogfr.2005.04.004

Kaplan SA, Cohen P (2007) The somatomedin hypothesis 2007: 50 years later. J Clin Endocrinol Metab 92(12):4529–4535. https://doi.org/10.1210/jc.2007-0526

Grimberg A, Cohen P (2000) Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 183(1):1–9

Khandwala H, Mccutcheon I, Flyvbjerg A (2000) The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 21(3):215–244

Pollak MN, Schernhammer ES, Hankinson SE (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4(7):505–518. https://doi.org/10.1038/nrc1387

Simmen FA, Badinga L, Green ML, Kwak I, Song S, Simmen RC (1998) The porcine insulin-like growth factor system: at the interface of nutrition, growth and reproduction. J Nutr 128(2 Suppl):315S

Brameld JM, Atkinson JL, Saunders JC, Pell JM, Buttery PJ, Gilmour RS (1996) Effects of growth hormone administration and dietary protein intake on insulin-like growth factor I and growth hormone receptor mRNA Expression in porcine liver, skeletal muscle, and adipose tissue. J Anim Sci 74(8):1832–1841

Oliver MH, Harding JE, Breier BH, Evans PC, Gluckman PD (1993) Glucose but not a mixed amino acid infusion regulates plasma insulin-like growth factor-I concentrations in fetal sheep. Pediatr Res 34:62. https://doi.org/10.1203/00006450-199307000-00015

Osborn BH, Fowlkes J, Han VK, Freemark M (1992) Nutritional regulation of insulin-like growth factor-binding protein gene expression in the ovine fetus and pregnant ewe. Endocrinology 131(4):1743–1750. https://doi.org/10.1210/endo.131.4.1382960

Olausson H, Sohlstrom A (2003) Effects of food restriction and pregnancy on the expression of insulin-like growth factors-I and -II in tissues from guinea pigs. J Endocrinol 179(3):437–445

Verkauskiene R, Jaquet D, Deghmoun S, Chevenne D, Czernichow P, Lévy-Marchal C (2005) Smallness for gestational age is associated with persistent change in insulin-like growth factor I (IGF-I) and the ratio of IGF-I/IGF-binding protein-3 in adulthood. J Clin Endocr Meta 90(10):5672–5676. https://doi.org/10.1210/jc.2005-0423

El-Khattabi I, Gregoire F, Remacle C, Reusens B (2003) Isocaloric maternal low-protein diet alters IGF-I, IGFBPs, and hepatocyte proliferation in the fetal rat. Am J Physiol Endocrinol Metab 285(5):E991–E1000. https://doi.org/10.1152/ajpendo.00037.2003

McNeil CJ, Hay SM, Rucklidge GJ, Reid MD, Duncan GJ, Rees WD (2009) Gene and protein expression profiles in the foetal liver of the pregnant rat fed a low protein diet. Genes Nutr 4(3):189–194. https://doi.org/10.1007/s12263-009-0125-6

Straus DS, Ooi GT, Orlowski CC, Rechler MM (1991) Expression of the genes for insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins-1 and -2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting. Endocrinology 128(1):518

Woodall SM, Breier BH, Johnston BM, Gluckman PD (1996) A model of intrauterine growth retardation caused by chronic maternal undernutrition in the rat: effects on the somatotrophic axis and postnatal growth. J Endocrinol 150(2):231–242

Woodall SM, Bassett NS, Gluckman PD, Breier BH (1998) Consequences of maternal undernutrition for fetal and postnatal hepatic insulin-like growth factor-I, growth hormone receptor and growth hormone binding protein gene regulation in the rat. J Mol Endocrinol 20(3):313–326

El-Khattabi I, Grégoire F, Remacle C, Reusens B (2003) Isocaloric maternal low-protein diet alters IGF-I, IGFBPs, and hepatocyte proliferation in the fetal rat. Am J Physiol Endocrinol Meta 285(5):E991

Denisenko O, Lin B, Louey S, Thornburg K, Bomsztyk K, Bagby S (2011) Maternal malnutrition and placental insufficiency induce global downregulation of gene expression in fetal kidneys. J Dev Orig Health Dis 2(2):124–133

Micke G, Sullivan T, Gatford K, Owens J, Perry V (2010) Nutrient intake in the bovine during early and mid-gestation causes sex-specific changes in progeny plasma IGF-I, liveweight, height and carcass traits. Anim Reprod Sci 121(3–4):208–217

Kalbe C, Lösel D, Block J, Lefaucheur L, Brüssow KP, Bellmann O, Pfuhl R, Puppe B, Otten W, Metges CC (2017) Moderate high or low maternal protein diets change gene expression but not the phenotype of skeletal muscle from porcine fetuses. Domest Anim Endocrinol 58:63–75

Geraghty AA, O’Brien EC, Alberdi G, Horan MK, Donnelly J, Larkin E, Segurado R, Mehegan J, Molloy EJ, McAuliffe FM (2018) Maternal protein intake during pregnancy is associated with child growth up to 5 years of age, but not through insulin-like growth factor-1: findings from the ROLO study. Br J Nutr 120(11):1252–1261. https://doi.org/10.1017/S0007114518002611

Vitale G, Pellegrino G, Vollery M, Hofland LJ (2019) Role of IGF-1 system in the modulation of longevity: controversies and new insights from a centenarians’ perspective. Front Endocrinol (Lausanne) 10:27. https://doi.org/10.3389/fendo.2019.00027

Tsukada A, Ohkubo T, Sakaguchi K, Tanaka M, Nakashima K, Hayashida Y, Wakita M, Hoshino S (1998) Thyroid hormones are involved in insulin-like growth factor-I (IGF-I) production by stimulating hepatic growth hormone receptor (GHR) gene expression in the chicken. Growth Horm IGF Res 8(3):235–242

Saenz de Miera C, Bothorel B, Jaeger C, Simonneaux V, Hazlerigg D (2017) Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland. Proc Natl Acad Sci USA 114(31):8408–8413. https://doi.org/10.1073/pnas.1702943114

Micke GC, Sullivan TM, Kennaway DJ, Hernandez-Medrano J, Perry VE (2015) Maternal endocrine adaptation throughout pregnancy to nutrient manipulation: consequences for sexually dimorphic programming of thyroid hormones and development of their progeny. Theriogenology 83(4):604–615. https://doi.org/10.1016/j.theriogenology.2014

Perks CM, Holly JM (2015) Epigenetic regulation of insulin-like growth factor binding protein-3 (IGFBP-3) in cancer. J Cell Commun Signal 9(2):159–166. https://doi.org/10.1007/s12079-015-0294-6

Nawathe AR, Christian M, Kim SH, Johnson M, Savvidou MD, Terzidou V (2016) Insulin-like growth factor axis in pregnancies affected by fetal growth disorders. Clinical epigenetics 8:11. https://doi.org/10.1186/s13148-016-0178-5

Jia Y, Cong R, Li R, Yang X, Sun Q, Parvizi N, Zhao R (2012) Maternal low-protein diet induces gender-dependent changes in epigenetic regulation of the glucose-6-phosphatase gene in newborn piglet liver. J Nutr 142(9):1659–1665. https://doi.org/10.3945/jn.112.160341

Cong R, Jia Y, Li R, Ni Y, Yang X, Sun Q, Parvizi N, Zhao R (2012) Maternal low-protein diet causes epigenetic deregulation of HMGCR and CYP7alpha1 in the liver of weaning piglets. J Nutr Biochem 23(12):1647–1654. https://doi.org/10.1016/j.jnutbio.2011.11.007

Suter MA, Ma J, Vuguin PM, Hartil K, Fiallo A, Harris RA, Charron MJ, Aagaard KM (2014) In utero exposure to a maternal high-fat diet alters the epigenetic histone code in a murine model. Am J Obstet Gynecol 210 (5):463 e461-463 e411, 10.1016/j.ajog.2014.01.045

Cai D, Yuan M, Jia Y, Liu H, Hu Y, Zhao R (2015) Maternal gestational betaine supplementation-mediated suppression of hepatic cyclin D2 and presenilin1 gene in newborn piglets is associated with epigenetic regulation of the STAT3-dependent pathway. J Nutr Biochem 26(12):1622–1631. https://doi.org/10.1016/j.jnutbio.2015.08.007

Cai D, Li H, Zhou B, Han L, Zhang X, Yang G (2012) Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue. Biochem Biophys Res Commun 422(4):621–626. https://doi.org/10.1016/j.bbrc.2012.05.038

Cai D, Wang J, Jia Y, Liu H, Yuan M, Dong H, Zhao R (2016) Gestational dietary betaine supplementation suppresses hepatic expression of lipogenic genes in neonatal piglets through epigenetic and glucocorticoid receptor-dependent mechanisms. Biochem Biophys Acta 1861(1):41–50. https://doi.org/10.1016/j.bbalip.2015

Jia Y, Gao G, Song H, Cai D, Yang X, Zhao R (2016) Low-protein diet fed to crossbred sows during pregnancy and lactation enhances myostatin gene expression through epigenetic regulation in skeletal muscle of weaning piglets. Eur J Nutr 55(3):1307–1314. https://doi.org/10.1007/s00394-015-0949-3

Metges CC, Gors S, Lang IS, Hammon HM, Brussow KP, Weitzel JM, Nurnberg G, Rehfeldt C, Otten W (2014) Low and high dietary protein:carbohydrate ratios during pregnancy affect materno-fetal glucose metabolism in pigs. J Nutr 144(2):155–163. https://doi.org/10.3945/jn.113.182691

Thompson AL, Lampl M (2013) Prenatal and postnatal energetic conditions and sex steroids levels across the first year of life. Am J Hum Biol 25(5):643–654. https://doi.org/10.1002/ajhb.22424

Reinehr T (2010) Obesity and thyroid function. Mol Cell Endocrinol 316(2):165–171. https://doi.org/10.1016/j.mce.2009.06.005

Mullur R, Liu YY, Brent GA (2014) Thyroid hormone regulation of metabolism. Physiol Rev 94(2):355–382. https://doi.org/10.1152/physrev.00030.2013

Liu G, Liang L, Bray GA, Qi L, Hu FB, Rood J, Sacks FM, Sun Q (2017) Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the pounds lost trial. Int J Obes (Lond) 41(6):878–886. https://doi.org/10.1038/ijo.2017.28

Switkowski KM, Jacques PF, Must A, Hivert M-F, Fleisch A, Gillman MW, Rifas-Shiman S, Oken E (2017) Higher maternal protein intake during pregnancy is associated with lower cord blood concentrations of insulin-like growth factor (IGF)-II, IGF binding protein 3, and insulin, but not IGF-I, in a cohort of women with high protein Intake. J Nutr 147(7):1392–1400. https://doi.org/10.3945/jn.117.250589

Osgerby JC, Wathes DC, Howard D, Gadd TS (2002) The effect of maternal undernutrition on ovine fetal growth. J Endocrinol 173(1):131–141

Igwebuike UM (2010) Impact of maternal nutrition on ovine foetoplacental development: a review of the role of insulin-like growth factors. Anim Reprod Sci 121(3–4):189–196. https://doi.org/10.1016/j.anireprosci.20

Singhal A (2017) Long-term adverse effects of early growth acceleration or catch-up growth. Ann Nutr Metab 70(3):236–240. https://doi.org/10.1159/000464302

Silveira PP, Pokhvisneva I, Gaudreau H, Rifkin-Graboi A, Broekman BFP, Steiner M, Levitan R, Parent C, Diorio J, Meaney MJ (2018) Birth weight and catch up growth are associated with childhood impulsivity in two independent cohorts. Sci Rep 8(1):13705. https://doi.org/10.1038/s41598-018-31816-5

Zhang DL, Du Q, Djemli A, Julien P, Fraser WD, Luo ZC (2017) Early and late postnatal accelerated growth have distinct effects on metabolic health in normal birth weight infants. Front Endocrinol (Lausanne) 8:340. https://doi.org/10.3389/fendo.2017.00340

Zheng J, Xiao X, Zhang Q, Wang T, Yu M, Xu J (2017) Maternal low-protein diet modulates glucose metabolism and hepatic microRNAs expression in the early life of offspring dagger. Nutrients. https://doi.org/10.3390/nu9030205

Brown A, Lee MD (2015) Early influences on child satiety-responsiveness: the role of weaning style. Pediatr Obes 10(1):57–66. https://doi.org/10.1111/j.2047-63

McOrist S, Mellits KH (2010) The important lifetime effects of intestinal gut health of pigs at weaning. Vet J 184(3):253–254. https://doi.org/10.1016/j.tvjl.2009.06.021

Cai D, Yuan M, Liu H, Pan S, Ma W, Hong J, Zhao R (2016) Maternal betaine supplementation throughout gestation and lactation modifies hepatic cholesterol metabolic genes in weaning piglets via AMPK/LXR-mediated pathway and histone modification. Nutrients. https://doi.org/10.3390/nu8100646

Ocklenburg S, Schmitz J, Moinfar Z, Moser D, Klose R, Lor S, Kunz G, Tegenthoff M, Faustmann P, Francks C, Epplen JT, Kumsta R, Gunturkun O (2017) Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries. eLife. https://doi.org/10.7554/elife.22784

Cai D, Jia Y, Lu J, Yuan M, Sui S, Song H, Zhao R (2014) Maternal dietary betaine supplementation modifies hepatic expression of cholesterol metabolic genes via epigenetic mechanisms in newborn piglets. Br J Nutr 112(9):1459–1468. https://doi.org/10.1017/S0007114514002402

Lee HS (2015) Impact of maternal diet on the epigenome during in utero life and the developmental programming of diseases in childhood and adulthood. Nutrients 7(11):9492–9507. https://doi.org/10.3390/nu7115467