Skip to main content
Log in

1H NMR-based metabolomics approach reveals metabolic alterations in response to dietary imbalances in Megalobrama amblycephala

  • Original Article
  • Published:
Metabolomics Aims and scope Submit manuscript

Abstract

Introduction

High-fat and high-carbohydrate diets cause a number of metabolic disorders in mammals. However, little is known about metabolomic changes caused by dietary imbalances in fish.

Objectives

The objective of this study was to assess the impacts of high-fat diet (HFD), high-carbohydrate diet (HCD) and high-fat-high-carbohydrate diet (HFHCD) on metabolites in a farmed cyprinid fish Megalobrama amblycephala.

Methods

We have employed the 1H NMR-based metabolomic approach to measure the concentrations of metabolites in plasma and liver of four different diet groups: HFD, HCD, HFHCD and control. Multivariate statistical analyses were used to determine significantly changed metabolites between all group-pairs.

Results

All three test diets have affected metabolic profiles, phenotypes and clinical chemistry. High-fat diets (HFD, HFHCD) resulted in a higher average weight than HCD, but high-carbohydrate diets (HCD, HFHCD) caused signs of liver damage. HCD has resulted in elevated metabolites in energy pathways, leading to further disturbances in creatine pathway. Excess of carbohydrate and lipid metabolism products in the HFHCD group appears to have caused “congestion” of the TCA cycle, causing a significant decline in the numbers of amino acids entering the cycle, which in turn resulted in elevated levels of seven amino acids in this group. Gut microbiota metabolites (TMA) exhibited a strong positive correlation with the carbohydrate content and a negative correlation with the fat content in diets.

Conclusion

These results provide an important insight into the diet-affected metabolic disorders that often lead to financial losses in the aquaculture of Megalobrama amblycephala.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Akhtar, M. T., Mushtaq, M. Y., Verpoorte, R., Richardson, M. K., & Choi, Y. H. (2016). Metabolic effects of cannabinoids in zebrafish (Danio rerio) embryos determined by 1H NMR metabolomics. Metabolomics, 12(3), 1–11. doi:10.1007/s11306-016-0964-2.

    Article  CAS  Google Scholar 

  • Allen, P. J., Wise, D., Greenway, T., Khoo, L., Griffin, M. J., & Jablonsky, M. (2015). Using 1-D 1 H and 2-D 1 H J-resolved NMR metabolomics to understand the effects of anemia in channel catfish (Ictalurus punctatus). Metabolomics, 11(5), 1131–1143. doi:10.1007/s11306-014-0767-2.

    Article  CAS  Google Scholar 

  • Al-Waiz, M., Mikov, M., Mitchell, S. C., & Smith, R. L. (1992). The exogenous origin of trimethylamine in the mouse. Metabolism, 41, 135–136.

    Article  Google Scholar 

  • An, Y., Xu, W., Li, H., Lei, H., Zhang, L., Hao, F., et al. (2013). High-fat diet induces dynamic metabolic alterations in multiple biological matrices of rats. Journal of Proteome Research, 12(8), 3755–3768. doi:10.1021/pr400398b.

    Article  CAS  PubMed  Google Scholar 

  • Anthoni, U., Børresen, T., Christophersen, C., Gram, L., & Nielsen, P. H. (1990). Is trimethylamine oxide a reliable indicator for the marine origin of fish. Comparative Biochemistry and Physiology Part B, 97(3), 569–571. doi:10.1016/0305-0491(90)90161-L.

    Article  Google Scholar 

  • Asai, A., Chou, P. M., Bu, H.-F., Wang, X., Rao, M. S., Jiang, A., et al. (2014). Dissociation of hepatic insulin resistance from susceptibility of nonalcoholic fatty liver disease induced by a high-fat and high-carbohydrate diet in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 306(6), G496–G504. doi:10.1152/ajpgi.00291.2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bunthawiyuwat, N. (2003). Energy Metabolism. In Nutritional biochemistry (pp. 179–180). Bangkok: Sigma Design Graphic.

    Google Scholar 

  • Dai, H., Xiao, C., Liu, H., Hao, F., & Tang, H. (2010). Combined NMR and LC-DAD-MS analysis reveals comprehensive metabonomic variations for three phenotypic cultivars of salvia miltiorrhiza bunge. Journal of Proteome Research, 9(3), 1565–1578. doi:10.1021/pr901045c.

    Article  CAS  PubMed  Google Scholar 

  • Dai, H., Xiao, C., Liu, H., & Tang, H. (2010). Combined NMR and LC-MS analysis reveals the metabonomic changes in salvia miltiorrhiza bunge induced by water depletion. Journal of Proteome Research, 9(3), 1460–1475. doi:10.1021/pr900995m.

    Article  CAS  PubMed  Google Scholar 

  • Duan, Y., An, Y., Li, N., Liu, B., Wang, Y., & Tang, H. (2013). Multiple univariate data analysis reveals the inulin effects on the high-fat-diet induced metabolic alterations in rat myocardium and testicles in the preobesity state. J Proteome Research, 12(7), 3480–3495. doi:10.1021/pr400341f.

    Article  CAS  Google Scholar 

  • Dumas, M. E., Barton, R. H., Toye, A., Cloarec, O., Blancher, C., Rothwell, A., et al. (2006). Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proceedings of the National Academy of Sciences, 103(33), 12511–12516. doi:10.1073/pnas.0601056103.

    Article  CAS  Google Scholar 

  • Dunn, W. B., Broadhurst, D. I., Atherton, H. J., Goodacre, R., & Griffin, J. L. (2011). Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chemical Society Reviews, 40(1), 387–426. doi:10.1039/b906712b.

    Article  CAS  PubMed  Google Scholar 

  • Erdei, N., Toth, A., Pasztor, E. T., Papp, Z., Edes, I., Koller, A., & Bagi, Z. (2006). High-fat diet-induced reduction in nitric oxide-dependent arteriolar dilation in rats: Role of xanthine oxidase-derived superoxide anion. American Journal of Physiology-Heart and Circulatory Physiology, 291, 2107–2115.

    Article  Google Scholar 

  • Eriksson, L., Trygg, J., & Wold, S. (2008). CV-ANOVA for significance testing of PLS and OPLS® models. Journal of Chemometrics, 22(11–12), 594–600. doi:10.1002/cem.1187.

    Article  CAS  Google Scholar 

  • Figueiredo-Silva, A. C., Panserat, S., Kaushik, S., Geurden, I., & Polakof, S. (2012). High levels of dietary fat impair glucose homeostasis in rainbow trout. Journal of Experimental Biology, 215(Pt 1), 169–178. doi:10.1242/jeb.063933.

    Article  CAS  PubMed  Google Scholar 

  • Food and Agriculture Organization of the United Nations. (2013). FAO statistical yearbook 2013†¯: World food and agriculture.

  • Gao, W., Liu, Y. J., Tian, L. X., Mai, K. S., Liang, G. Y., Yang, H. J., et al. (2009). Effect of dietary carbohydrate-to-lipid ratios on growth performance, body composition, nutrient utilization and hepatic enzymes activities of herbivorous grass carp (Ctenopharyngodon idella). Aquaculture Nutrition, 16(3), 327–333. doi:10.1111/j.1365-2095.2009.00668.x.

    Article  Google Scholar 

  • Ge, C. X., Yu, R., Xu, M. X., Li, P. Q., Fan, C. Y., Li, J. M., & Kong, L. D. (2016). Betaine prevented fructose-induced NAFLD by regulating LXα/PPARα pathway and alleviating ER stress in rats. European Journal of Pharmacology, 770, 154–164. doi:10.1016/j.ejphar.2015.11.043.

    Google Scholar 

  • Hellerstein, M. K. (1999). De novo lipogenesis in humans: metabolic and regulatory aspects. European Journal of Clinical Nutrition, 53(s1), S53–65. doi:10.1038/SJ.EJCN.1600744.

    Article  PubMed  Google Scholar 

  • Hemre, G. I., Mommsen, T. P., & Krogdahl, Å (2002). Carbohydrates in fish nutrition: Effects on growth, glucose metabolism and hepatic enzymes. Aquaculture Nutrition, 8(3), 175–194. doi:10.1046/j.1365-2095.2002.00200.x.

    Article  CAS  Google Scholar 

  • Horton, T. J., Drougas, H., Brachey, A., Reed, G. W., Peters, J. C., & Hill, J. O. (1995). Fat and carbohydrate overfeeding in humans: different effects on energy storage. The American Journal of Clinical Nutrition, 62, 19–29.

    CAS  PubMed  Google Scholar 

  • Jiang, Y., Yang, M., Yang, L., Miao, X., Wang, H., & Zhu, B. (2013). A 1H NMR-BASED metabonomic investigation of time- related metabolic trajectories of the plasma, urine and liver extracts of hyperlipidemic hamsters. PLoS One, 8, E66786. doi:10.1371/journal.pone.0066786.t001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung, J. Y., Kim, I. Y., Kim, Y. N., Kim, J. S., Shin, J. H., Jang, Z. H., et al. (2012). 1H NMR-based metabolite profiling of diet-induced obesity in a mouse model. BMB Reports, 45(7), 419–424. doi:10.5483/BMBRep.2012.45.7.248.

    Article  CAS  PubMed  Google Scholar 

  • Kim, I. Y., Jung, J., Jang, M., Ahn, Y. G., Shin, J. H., Choi, J. W., et al. (2010). 1H NMR-based metabolomic study on resistance to diet-induced obesity in AHNAK knock-out mice. Biochemical and Biophysical Research Communications, 403(3–4), 428–434. doi:10.1016/j.bbrc.2010.11.048.

    Article  CAS  PubMed  Google Scholar 

  • Koteish, A., & Diehl, A. M. (2001). Animal models of steatosis. Seminars in Liver Disease, 21(1), 89–104. doi:10.1055/s-2001-12932.

    Article  CAS  PubMed  Google Scholar 

  • Kullgren, A., Samuelsson, L. M., Larsson, D. G., Bjornsson, B. T., & Bergman, E. J. (2010). A metabolomics approach to elucidate effects of food deprivation in juvenile rainbow trout (Oncorhynchus mykiss). American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 299(6), R1440–R1448. doi:10.1152/ajpregu.00281.2010.

    Article  CAS  PubMed  Google Scholar 

  • Lever, M., & Slow, S. (2010). The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clinical Biochemistry, 43(9), 732–744. doi:10.1016/j.clinbiochem.2010.03.009.

    Article  CAS  PubMed  Google Scholar 

  • Li, H., Wu, S., Wirth, S., Hao, Y., Wang, W., Zou, H., et al. (2016). Diversity and activity of cellulolytic bacteria, isolated from the gut contents of grass carp (Ctenopharyngodon idellus) (Valenciennes) fed on Sudan grass (Sorghum sudanense) or artificial feedstuffs. Aquaculture Research, 47(1), 153–164. doi:10.1111/are.12478.

    Article  CAS  Google Scholar 

  • Li, X. F., Liu, W. B., Lu, K. L., Xu, W. N., & Wang, Y. (2012). Dietary carbohydrate/lipid ratios affect stress, oxidative status and non-specific immune responses of fingerling blunt snout bream, Megalobrama amblycephala. Fish Shellfish Immunol, 33(2), 316–323. Journal Article. doi:10.1016/j.fsi.2012.05.007.

    Google Scholar 

  • Li, X. F., Lu, K. L., Liu, W. B., Jiang, G. Z., & Xu, W. N. (2014). Effects of dietary lipid and carbohydrate and their interaction on growth performance and body composition of Juvenile Blunt Snout Bream, Megalobrama amblycephala. The Israeli Journal of Aquaculture - Bamidgeh, 66, 1–7.

  • Li, X. F., Wang, Y., Liu, W. B., Jiang, G. Z., & Zhu, J. (2013). Effects of dietary carbohydrate/lipid ratios on growth performance, body composition and glucose metabolism of fingerling blunt snout bream Megalobrama amblycephala. Aquaculture Nutrition, 19(5), 701–708. doi:10.1111/anu.12017.

    Article  CAS  Google Scholar 

  • Ni, J., Yan, Q., Yu, Y., & Zhang, T. (2014). Factors influencing the grass carp gut microbiome and its effect on metabolism. FEMS Microbiology Ecology, 87(3).

  • Ong, E. S., Chor, C. F., Zou, L., & Ong, C. N. (2009). A multi-analytical approach for metabolomic profiling of zebrafish (Danio rerio) livers. Molecular bioSystems, 5(3), 288–298. doi:10.1039/b811850g.

    Article  CAS  PubMed  Google Scholar 

  • Owen, L., & Sunram-Lea, S. I. (2011). Metabolic agents that enhance ATP can improve cognitive functioning: A review of the evidence for glucose, oxygen, pyruvate, creatine, and l-carnitine. Nutrients. doi:10.3390/nu3080735.

    PubMed  PubMed Central  Google Scholar 

  • Peng, J. B., Jia, H. M., Xu, T., Liu, Y. T., Zhang, H. W., Yu, L. L., et al. (2011). A 1H NMR based metabonomics approach to progression of coronary atherosclerosis in a rabbit model. Process Biochemistry (Oxford, U. K.), 46(12), 2240–2247. doi:10.1016/j.procbio.2011.08.016.

    Article  CAS  Google Scholar 

  • Polakof, S., Medale, F., Larroquet, L., Vachot, C., Corraze, G., & Panserat, S. (2011). Regulation of de novo hepatic lipogenesis by insulin infusion in rainbow trout fed a high-carbohydrate diet. J. Anim. Sci., 89(10), 3079–3088. doi:10.2527/jas.2010-3733.

    Article  CAS  PubMed  Google Scholar 

  • Qiu, L., Song, Q., Jiang, X., Zhao, H., Chen, H., Zhou, H., et al. (2016). Comparative gonad protein and metabolite responses to a binary mixture of 2,4′-DDT and benzo(a)pyrene in the female green mussel Perna viridis. Metabolomics, 12(8), 140. doi:10.1007/s11306-016-1089-3.

    Article  Google Scholar 

  • Ren, M., Habte-Tsion, H. M., Xie, J., Liu, B., Zhou, Q., Ge, X., et al. (2015). Effects of dietary carbohydrate source on growth performance, diet digestibility and liver glucose enzyme activity in blunt snout bream, Megalobrama amblycephala. Aquaculture, 438, 75–81. doi:10.1016/j.aquaculture.2015.01.008.

    Article  CAS  Google Scholar 

  • Schock, T. B., Newton, S., Brenkert, K., Leffler, J., & Bearden, D. W. (2012). An NMR-based metabolomic assessment of cultured cobia health in response to dietary manipulation. Food Chem., 133(1), 90–101. doi:10.1016/j.foodchem.2011.12.077.

    Article  CAS  Google Scholar 

  • Schwarz, J. M., Noworolski, S. M., Wen, M. J., Dyachenko, A., Prior, J. L., Weinberg, M. E., et al. (2015). Effect of a high-fructose weight-maintaining diet on lipogenesis and liver fat. Journal of Clinical Endocrinology and Metabolism, 100(6), 2434–2442. doi:10.1210/jc.2014-3678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shanware, N. P., Mullen, A. R., DeBerardinis, R. J., & Abraham, R. T. (2011). Glutamine: Pleiotropic roles in tumor growth and stress resistance. Journal of Molecular Medicine. doi:10.1007/s00109-011-0731-9.

    PubMed  Google Scholar 

  • Shao, Y., Li, C., Chen, X., Zhang, P., Li, Y., Li, T., & Jiang, J. (2015). Metabolomic responses of sea cucumber Apostichopus japonicus to thermal stresses. Aquaculture. doi:10.1016/j.aquaculture.2014.10.023.

    Google Scholar 

  • Shi, X., Xiao, C., Wang, Y., & Tang, H. (2013). Gallic acid intake induces alterations to systems metabolism in rats. Journal of Proteome Research, 12(2), 991–1006. doi:10.1021/pr301041k.

    Article  CAS  PubMed  Google Scholar 

  • Shimeno, S., Ming, D.-C., & Takeda, M. (1993). Metabolic response to dietary carbohydrate to lipid ratios in Oreochromis niloticus. NIPPON SUISAN GAKKAISHI, 59(5), 827–833. doi:10.2331/suisan.59.827.

    Article  CAS  Google Scholar 

  • Shimomura, Y., Murakami, T., Nakai, N., Nagasaki, M., & Harris, R. A. (2004). Exercise promotes BCAA catabolism: Effects of BCAA supplementation on skeletal muscle during exercise. The Journal of Nutrition, 134(6), 1583S–1587.

    CAS  PubMed  Google Scholar 

  • Spencer, M. D., Hamp, T. J., Reid, R. W., Fischer, L. M., Zeisel, S. H., & Fodor, A. A. (2011). Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology, 140(3), 976–986. doi:10.1053/j.gastro.2010.11.049.

    Article  CAS  PubMed  Google Scholar 

  • Toborek, M., Kopieczna-Grzebieniak, E., Marian Drózdz, M., & Wieczorek, M. (1995). Increased lipid peroxidation as a mechanism of methionine-induced atherosclerosis in rabbits. Atherosclerosis, 115(2), 217–224. doi:10.1016/0021-9150(94)05516-L.

    Article  CAS  PubMed  Google Scholar 

  • Wagner, L., Trattner, S., Pickova, J., Gómez-Requeni, P., & Moazzami, A. A. (2014). 1H NMR-based metabolomics studies on the effect of sesamin in Atlantic salmon (Salmo salar). Food Chemistry, 147, 98–105. doi:10.1016/j.foodchem.2013.09.128.

    Article  CAS  PubMed  Google Scholar 

  • Wang, X. D., Li, E. C., Wang, S. F., Qin, J. G., Chen, X. F., Lai, Q. M., et al. (2015). Protein-sparing effect of carbohydrate in the diet of white shrimp Litopenaeus vannamei at low salinity. Aquaculture Nutrition, 21(6), 904–912. doi:10.1111/anu.12221.

    Article  CAS  Google Scholar 

  • Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., Dugar, B., et al. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57–63. doi:10.1038/nature09922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wyss, M., & Daouk, R. K. (2000). Creatine and creatinine metabolism. Physiological Reviews, 80(3), 1107–1213.

    CAS  PubMed  Google Scholar 

  • Xie, Z., Li, H., Wang, K., Lin, J., Wang, Q., Zhao, G., et al. (2010). Analysis of transcriptome and metabolome profiles alterations in fatty liver induced by high-fat diet in rat. Metabolism, 59(4), 554–560. doi:10.1016/j.metabol.2009.08.022.

    PubMed  Google Scholar 

  • Yamashita, H., Takenoshita, M., Sakurai, M., Bruick, R. K., Henzel, W. J., Shillinglaw, W., et al. (2001). A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proceedings of the National Academy of Sciences of the United States of America, 98(16), 9116–9121. doi:10.1073/pnas.161284298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yelamanchi, S. D., Jayaram, S., Thomas, J. K., Gundimeda, S., Khan, A. A., Singhal, A., et al. (2016). A pathway map of glutamate metabolism. Journal of Cell Communication and Signaling, 10(1), 69–75. doi:10.1007/s12079-015-0315-5.

    Article  PubMed  Google Scholar 

  • Yki-Järvinen, H., Bogardus, C., & Howard, B. V. (1987). Hyperglycemia stimulates carbohydrate oxidation in humans. The American Journal of Physiology, 253(4 Pt 1), E376–E382.

    PubMed  Google Scholar 

  • Yoshimatsu, H., Tsuda, K., Niijima, A., Tatsukawa, M., Chiba, S., & Sakata, T. (2002). Histidine induces lipolysis through sympathetic nerve in white adipose tissue. European Journal of Clinical Investigation, 32, 236–241.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, X., Wu, C., Peng, X., & Li, H. (2014). Interferon-α2b against microbes through promoting biosynthesis of unsaturated fatty acids. Journal of Proteome Research, 13(9), 4155–4163. doi:10.1021/pr500592x.

    Article  CAS  PubMed  Google Scholar 

  • Zhou, C. P., Ge, X. P., Liu, B., Xie, J., & Miao, L. H. (2013). Effect of high dietary carbohydrate on the growth performance and physiological responses of juvenile wuchang bream, Megalobrama amblycephala. Asian-Australasian Journal of Animal Sciences, 26(11), 1598–1608. doi:10.5713/ajas.2012.12659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by Natural Science Foundation of China (No. 31401976), the earmarked fund for the Fundament Research Funds for the Central Universities (2662015PY019) and Modern Agro-industry Technology Research System entitled ‘‘Staple Freshwater Fishery Industry Technology System’’ (No.CARS-46-05).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yu-Hua Zhao or Wei-Min Wang.

Ethics declarations

Conflict of interest

The authors have declared that no conflict of interest exists.

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material (DOCX 1775 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Prathomya, P., Prisingkorn, W., Jakovlić, I. et al. 1H NMR-based metabolomics approach reveals metabolic alterations in response to dietary imbalances in Megalobrama amblycephala . Metabolomics 13, 17 (2017). https://doi.org/10.1007/s11306-016-1158-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11306-016-1158-7

Keywords

Navigation