Explorative study of metabolic adaptations to various dietary calcium intakes and cereal sources on serum metabolome and hepatic gene expression in juvenile pigs
- 321 Downloads
Daily calcium (Ca) intake is critical for bone health and energy metabolism, but less is known about its metabolic role at young ages. We used targeted electrospray ionization liquid chromatography–mass spectrometry-based metabolomics and candidate gene expression to compare the effect of dietary Ca level (high vs. adequate intake), as influenced by dietary cereal composition (wheat–barley vs. corn grains), on postprandial serum metabolome profiles and hepatic expression of genes related to glucose, lipid and amino acid metabolism in juvenile pigs (n = 32; 7-weeks of age). Explorative analysis of 132 metabolites demonstrated that postprandial serum of pigs fed high Ca contained greater (p < 0.05) concentrations of hexoses, 13 amino acids, 3 polyamines and 33 phosphatidylcholines compared to pigs fed adequate Ca. Partial-least-squares-discriminant analysis and cereal–Ca interactions indicated that the dietary cereal source may modulate the metabolic Ca response to a meal. Hepatic responses showed trends for upregulation of PPARG and SRBEF1 expression with high versus adequate Ca diets. Present data are consistent with the concept that dietary Ca modifies systemic metabolic processes in young animals. Targeted metabolomics provided greater insight into the complex metabolic responses related to dietary Ca than previously reported.
KeywordsHigh-calcium diet Dietary cereals Serum metabolome Hepatic gene expression Juvenile pigs
This research was supported by the Profile Lines of the University of Veterinary Medicine Vienna (Start-up project “PL Effects of Ca in weaned pigs” to B.U.M.Z.). We thank A. Dockner, M. Wild, R. Rick (Institute of Animal Nutrition and Functional Plant Compounds), E. Mann (Institute of Milk Hygiene, University of Veterinary Medicine Vienna), M. Adib Razavi (VetCore Facility for Research) and the staff of the Clinic for Swine for assistance with sampling and analyses. Our thanks are extended to E. Schneeberger (GARANT Tiernahrung, Pöchlarn, Austria) for diet preparation.
Conflict of interest
All authors declare no conflict of interest.
- Chow, J., Panasevich, M. R., Alexander, D., Vester Boler B. M., Rossoni Serao, M. C., Faber, T. A., et al. (2014). Fecal metabolomics of healthy breast-fed versus formula-fed infants before and during in vitro batch culture fermentation. Journal of Proteome Research (in press). doi: 10.1021/pr500011w.
- Claessens, M., Saris, W. H., & van Baak, M. A. (2008). Glucagon an dinsulin responses after ingestion of different amounts of intact and hydrolysed proteins. British Journal of Nutrition, 11, 61–69.Google Scholar
- Crenshaw, T. D. (1995). Calcium, phosphorus, vitamin D, and vitamin K in swine nutrition. In A. J. Lewis & L. L. Southern (Eds.), Swine nutrition (2nd ed., pp. 187–212). Boca Raton, FL: CRC Press.Google Scholar
- Fan, Y., Guo, Y., Hamblin, M., Chang, L., Zhang, J., & Chen, Y. E. (2011). Inhibition of gluconeogenic genes by calcium-regulated heat-stable protein 1 via repression of peroxisome proliferator-activated receptor α. Journal of Biological Chemistry, 286, 40584–40595.CrossRefPubMedCentralPubMedGoogle Scholar
- Fehlmann, M., & Freychet, P. (1981). Insulin and glucagon stimulation of (Na+–K+)-ATPase transport activity in isolated rat hepatocytes. Journal of Biological Chemistry, 266, 7449–7458.Google Scholar
- GfE [Gesellschaft für Ernährungsphysiologie]. (2006). Empfehlungen zur Energie- und Nährstoffversorgung von Schweinen. Frankfurt am Main: DLG-Verlag.Google Scholar
- Giacco, R., Costabile, G., Della Pepa, G., Anniballi, G., Griffo, E., Mangione, A., et al. (2014). A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome. Nutrition, Metabolism, Cardiovascular Diseases (in press). doi: 10.1016/j.numecd.2014.01.007.
- Lillefosse, H. H., Clausen, M. R., Yde, C. C., Ditlev, D. B., Zhang, X., Du, Z. Y., et al. (2014). Urinary loss of tricarboxylic acid cycle intermediates as revealed by metabolomics studies—an underlying mechanism to reduce lipid accretion by whey protein ingestion? Journal of Proteome Research (in press). doi: 10.1021/pr500039t.
- Lopes Nobre, J., Lisboa, P. C., da Silva Lima, N., Franco, J. G., Firmino Noqueira Neto, J., de Moura, E. G., et al. (2012). Calcium supplementation prevents obesity, hyperleptinaemia and hyperglycaemia in adult rats programmed by early weaning. British Journal Nutrition, 107, 979–988.CrossRefGoogle Scholar
- Lynch, C. J., McCall, K. M., Ng, Y. C., & Hazen, S. A. (1996). Glucagon stimulation of hepatic Na(+)-pump activity and alpha-subunit phosphorylation in rat hepatocytes. Biochemistry Journal, 313, 983–989.Google Scholar
- Metzler-Zebeli, B. U., Hooda, S., Mosenthin, R., Gänzle, M. G., & Zijlstra, R. T. (2010). Bacterial fermentation affects net mineral flux in the large intestine of pigs fed diets with viscous and fermentable non-starch polysaccharides. Journal of Animal Science, 88, 3351–3362.CrossRefPubMedGoogle Scholar
- Metzler-Zebeli, B. U., Mann, E., Schmitz-Esser, S., Wagner, M., Ritzmann, M., & Zebeli, Q. (2013b). Gastrointestinal microbiota and metabolites respond differently to high dietary calcium–phosphorus level in weaned pigs fed various cereal sources. Applied and Environmental Microbiology, 79, 7264–7272.CrossRefPubMedCentralPubMedGoogle Scholar
- Michal, G. (1999). Biochemical pathways: An atlas of biochemistry and molecular biology. Heidelberg: Spektrum Akademischer Verlag.Google Scholar
- Murgas Torrazza, R., Suryawan, A., Gazzaneo, M. C., Orellana, R. A., Frank, J. W., Nguyen, H. V., et al. (2010). Leucine supplementation of a low-protein meal increases skeletal muscle and visceral tissue protein synthesis in neonatal pigs by stimulating mTOR-dependent translation initiation. Journal of Nutrition, 140, 2145–2152.CrossRefPubMedCentralPubMedGoogle Scholar
- Nebendahl, C., Krüger, R., Görs, S., Albrecht, E., Martens, K., Hennig, S., et al. (2013). Effects on transcriptional regulation and lipid droplet characteristics in the liver of female juvenile pigs after early postnatal feed restriction and refeeding are dependent on birth weight. PLoS ONE, 8, e76705.CrossRefPubMedCentralPubMedGoogle Scholar
- Nørskov, N. P., Hedemann, M. S., Lærke, H. N., & Bach Knudsen, K. E. (2013). Multicompartmental nontargeted LC-MS metabolomics: Explorative study on the metabolic responses of rye fiber versus refined wheat fiber intake in plasma and urine of hypercholesterolemic pigs. Journal of Proteome Research, 12, 2818–2832.CrossRefPubMedGoogle Scholar
- NRC (Nutrient Research Council). (1998). Nutrient requirements of swine (10th ed.). Washington, DC: National Academic Press.Google Scholar
- O’Connor, P. M., Kimball, S. R., Suryawan, A., Bush, J. A., Nguyen, H. V., Jefferson, L. S., et al. (2003). Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs. American Journal of Physiology, Endocrinology and Metabolism, 285, E40–E53.CrossRefGoogle Scholar
- Suryawan, A., Torrazza, R. M., Gazzaneo, M. C., Orellana, R. A., Fiorotto, M. L., El-Kadi, S. W., et al. (2012). Enteral leucine supplementation increases protein synthesis in skeletal and cardiac muscles and visceral tissues of neonatal pigs through mTORC1-dependent pathways. Pediatric Research, 71, 324–331.CrossRefPubMedCentralPubMedGoogle Scholar
- Torres-Fuentes, C., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2014). A natural solution for obesity: Bioactives for the prevention and treatment of weight gain. A review. Nutritional Neuroscience. doi: 10.1179/1476830513Y.0000000099.
- Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., van Roy, N., de Paepe, A., et al. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology, 3, RESEARCH0034.Google Scholar
- VDLUFA. (1976). Methodenbuch. Buch III: Die chemische Untersuchung von Futtermitteln (3rd ed.). Darmstadt: VDLUFA-Verlag.Google Scholar
- Wilson, G. J., Layman, D. K., Moulton, C. J., Norton, L. E., Anthony, T. G., Proud, C. G., et al. (2011). Leucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats. American Journal of Physiology, Endocrinology and Metabolism, 301, E1236–E1242.CrossRefGoogle Scholar