Skip to main content

Advertisement

SpringerLink
Log in

Multivariate statistical analysis of metabolomics profiles in tissues of polar bears (Ursus maritimus) from the Southern and Western Hudson Bay subpopulations

  • Original Paper
  • Published:
Polar Biology Aims and scope Submit manuscript

Abstract

Polar bears (Ursus maritimus) are apex predators of the Arctic, which exposes them to an array of natural and anthropogenic stress factors. Metabolomics analysis profiles endogenous metabolites that reflect the response of biological systems to stimuli, and the effects of multiple stressors can be assessed from an integrated perspective. A targeted, quantitative, liquid chromatography–mass spectrometry-based metabolomics platform [219 metabolites including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines (PCs), sphingomyelins, hexoses (Hex), and fatty acids (FAs)] was applied to the muscle and liver of polar bears from the Southern and Western Hudson Bay (Canada) subpopulations (SHB and WHB, respectively). Multivariate statistics were then applied to establish whether bears were discriminated by sex and/or subpopulation. Five metabolites identified by variable importance projection (VIP) discriminated the hepatic profiles of SHB males and females (Hex, arginine, glutamine, one PC, one sphingomyelin), while fifteen metabolites (primarily PCs along with leucine) contrasted the livers of males from SHB and WHB. Metabolite profiles in the muscle of male and female bears could not be differentiated; however, the muscles of SHB and WHB males were discriminated primarily by PCs and FAs. Stable isotope ratios (δ13C and δ15N) were variably related to metabolites; δ13C was correlated with some VIP metabolite concentrations, particularly in comparisons of male bears from SHB and WHB, suggesting an influence of dietary differences. However, δ15N and age exhibited few, relatively weak correlations with metabolites. The metabolite profiles discriminating the sexes and subpopulations may have utility for future assessments regarding the effects of specific stressors on the physiology of Hudson Bay polar bears.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aliferis KA, Chrysayi-Tokousbalides M (2011) Metabolomics in pesticide research and development: review and future perspectives. Metabolomics 7:35–53. doi:10.1007/s11306-010-0231-x

    Article  CAS  Google Scholar 

  • Alonso A, Marsal S, Julia A (2015) Analytical methods in untargeted metabolomics: state of the art in 2015. Front Bioeng Biotechnol 3:1–20. doi:10.3389/fbioe.2015.00023

    Article  Google Scholar 

  • Asuero A, Sayago A, González AG (2006) The correlation coefficient: an overview. Crit Rev Anal Chem 36:41–59

    Article  CAS  Google Scholar 

  • Benskin JP, Ikonomou MG, Liu J, Veldhoen N, Dubetz C, Helbing CC, Cosgrove JR (2014) Distinctive metabolite profiles in in-migrating sockeye salmon suggest sex-linked endocrine perturbation. Environ Sci Technol 48:11670–11678. doi:10.1021/es503266x

    Article  CAS  PubMed  Google Scholar 

  • Bertolo RF, Burrin DG (2008) Comparative aspects of tissue glutamine and proline metabolism. J Nutr 138:2032S–2039S

    Article  CAS  PubMed  Google Scholar 

  • Bertram HC et al (2009) Nuclear magnetic resonance-based metabonomics reveals strong sex effect on plasma metabolism in 17-year-old Scandinavians and correlation to retrospective infant plasma parameters. Metab Clin Exp 58:1039–1045. doi:10.1016/j.metabol.2009.03.011

    Article  CAS  PubMed  Google Scholar 

  • Boertje RD, Ellis MM, Kellie KA (2015) Accuracy of moose age determinations from canine and incisor cementum annuli. Wildl Soc B 39:383–389. doi:10.1002/wsb.537

    Article  Google Scholar 

  • Brunborg LA, Julshamn K, Nortvedt R, Frøyland L (2006) Nutritional composition of blubber and meat of hooded seal (Cystophora cristata) and harp seal (Phagophilus groenlandicus) from Greenland. Food Chem 96:524–531. doi:10.1016/j.foodchem.2005.03.005

    Article  CAS  Google Scholar 

  • Buang Y, Wang YM, Cha JY, Nagao K, Yanagita T (2005) Dietary phosphatidylcholine alleviates fatty liver induced by orotic acid. Nutrition 21:867–873. doi:10.1016/j.nut.2004.11.019

    Article  CAS  PubMed  Google Scholar 

  • Bundy JG, Davey MP, Viant MR (2009) Environmental metabolomics: a critical review and future perspectives. Metabolomics 5:3–21. doi:10.1007/s11306-008-0152-0

    Article  CAS  Google Scholar 

  • Cai X, Li R (2016) Concurrent profiling of polar metabolites and lipids in human plasma using HILIC-FTMS. Sci Rep 6:36490. doi:10.1038/srep36490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Christie W (2016) Phosphatidylcholine. The American Oil Chemists Society. http://lipidlibrary.aocs.org/Primer/content.cfm?ItemNumber=39351. Accessed 14 Dec 2016

  • Clarke CJ, Haselden JN (2008) Metabolic profiling as a tool for understanding mechanisms of toxicity. Toxicol Pathol 36:140–147. doi:10.1177/0192623307310947

    Article  CAS  PubMed  Google Scholar 

  • Colby HD (1980) Regulation of hepatic drug and steroid metabolism by androgens and estrogens. Adv Sex Horm Res 4:27–71

    CAS  Google Scholar 

  • Cole LK, Vance JE, Vance DE (2012) Phosphatidylcholine biosynthesis and lipoprotein metabolism. Biochim Biophys Acta 1821:754–761. doi:10.1016/j.bbalip.2011.09.009

    Article  CAS  PubMed  Google Scholar 

  • Committee on the Status of Endangered Wildlife in Canada (COSEWIC) (2008) COSEWIC assessment and update status report on the polar bear (Ursus maritimus) in Canada. COSEWIC, Ottawa

  • Derocher AE, Lunn NJ, Stirling I (2004) Polar bears in a warming climate. Integr Comp Biol 44:163–176. doi:10.1093/icb/44.2.163

    Article  PubMed  Google Scholar 

  • Derocher AE, Andersen M, Wiig Ø (2005) Sexual dimorphism of polar bears. J Mammal 86:895–901. doi:10.1644/1545-1542(2005)86[895:SDOPB]2.0.CO;2

  • Dunn WB, Ellis DI (2005) Metabolomics: current analytical platforms and methodologies. Trends Anal Chem 24:285–294. doi:10.1016/j.trac.2004.11.021

    Article  CAS  Google Scholar 

  • Ekroos K, Ejsing CS, Bahr U, Karas M, Simons K, Shevchenko A (2003) Charting molecular composition of phosphatidylcholines by fatty acid scanning and ion trap MS3 fragmentation. J Lipid Res 44:2181–2192. doi:10.1194/jlr.D300020-JLR200

    Article  CAS  PubMed  Google Scholar 

  • Ellis RP, Spicer JI, Byrne JJ, Sommer U, Viant MR, White DA, Widdicombe S (2014) 1H NMR metabolomics reveals contrasting response by male and female mussels exposed to reduced seawater pH, increased temperature, and a pathogen. Environ Sci Technol 48:7044–7052. doi:10.1021/es501601w

    Article  CAS  PubMed  Google Scholar 

  • Environment and Climate Change Canada (ECCC) (2014) Maps of global and Canadian sub-populations of polar bears and protected areas. ECCC. https://www.ec.gc.ca/nature/default.asp?lang=En&n=F77294A3-1. Accessed 18 Jul 2016

  • Gormezano LJ, Rockwell RF (2013a) Dietary composition and spatial patterns of polar bear foraging on land in western Hudson Bay. BMC Ecol 13:51. doi:10.1186/1472-6785-13-51

    Article  PubMed  PubMed Central  Google Scholar 

  • Gormezano LJ, Rockwell RF (2013b) What to eat now? Shifts in polar bear diet during the ice-free season in western Hudson Bay. Ecol Evol 3:3509–3523. doi:10.1002/ece3.740

    PubMed  PubMed Central  Google Scholar 

  • Hanamatsu H et al (2014) Altered levels of serum sphingomyelin and ceramide containing distinct acyl chains in young obese adults. Nutr Diabetes 4:e141. doi:10.1038/nutd.2014.38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen BH, Degnes K, Øverjordet IB, Altin D, Størseth TR (2013) Metabolic fingerprinting of arctic copepods Calanus finmarchicus, Calanus glacialis and Calanus hyperboreus. Polar Biol 36:1577–1586

    Article  Google Scholar 

  • Hensel RJ, Sorensen FE (1980) Age determination of live polar bears. Bears 4:93–100

    Google Scholar 

  • Hines A, Oladiran GS, Bignell JP, Stentiford GD, Viant MR (2007) Direct sampling of organisms from the field and knowledge of their phenotype: key recommendations for environmental metabolomics. Environ Sci Technol 41:3375–3381

    Article  CAS  PubMed  Google Scholar 

  • Hobson KA, Welch HE (1992) Determination of trophic relationships within a high Arctic food web using δ13C and δ15 N anaylsis. Mar Ecol Prog Ser 84:9–18

    Article  CAS  Google Scholar 

  • Huang SS, Benskin JP, Chandramouli B, Butler H, Helbing CC, Cosgrove JR (2016) Xenobiotics produce distinct metabolomic responses in zebrafish larvae (Danio rerio). Environ Sci Technol 50:6526–6535. doi:10.1021/acs.est.6b01128

    Article  CAS  PubMed  Google Scholar 

  • Huang SSY, Benskin JP, Veldhoen N, Chandramouli B, Butler H, Helbing CC, Cosgrove JR (2017) A multi-omic approach to elucidate low-dose effects of xenobiotics in zebrafish (Danio rerio) larvae. Aquat Toxicol 182:102–112. doi:10.1016/j.aquatox.2016.11.016

    Article  CAS  PubMed  Google Scholar 

  • Idle JR, Gonzalez FJ (2007) Metabolomics. Cell Metab 6:348–351. doi:10.1016/j.cmet.2007.10.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelly JF (2000) Stable isotopes of carbon and nitrogen in the study of avian and mammalian trophic ecology. Can J Zool 78:1–27

    Article  Google Scholar 

  • Kochhar S, Jacobs DM, Ramadan Z, Berruex F, Fuerholz A, Fay LB (2006) Probing gender-specific metabolism differences in humans by nuclear magnetic resonance-based metabonomics. Anal Biochem 352:274–281. doi:10.1016/j.ab.2006.02.033

    Article  CAS  PubMed  Google Scholar 

  • Laidre KL, Born EW, Gurarie E, Wiig O, Dietz R, Stern H (2013) Females roam while males patrol: divergence in breeding season movements of pack-ice polar bears (Ursus maritimus). Proc Biol Sci 280:20122371. doi:10.1098/rspb.2012.2371

    Article  PubMed  PubMed Central  Google Scholar 

  • Letcher RJ, Gebbink WA, Sonne C, Born EW, McKinney MA, Dietz R (2009) Bioaccumulation and biotransformation of brominated and chlorinated contaminants and their metabolites in ringed seals (Pusa hispida) and polar bears (Ursus maritimus) from East Greenland. Environ Int 35:1118–1124. doi:10.1016/j.envint.2009.07.006

    Article  CAS  PubMed  Google Scholar 

  • Letcher RJ et al (2010) Exposure and effects assessment of persistent organohalogen contaminants in arctic wildlife and fish. Sci Total Environ 408:2995–3043. doi:10.1016/j.scitotenv.2009.10.038

    Article  CAS  PubMed  Google Scholar 

  • Lin CY, Viant MR, Tjeerdema RS (2006) Metabolomics: methodologies and applications in the environmental sciences. J Pestic Sci 31:245–251

    Article  CAS  Google Scholar 

  • Matson G, Van Daele L, Goodwin E, Aumiller L, Reynolds H, Hristienko H (1993) A laboratory manual for cementum age determination of Alaska brown bear first premolar teeth. Alaska Department of Fish and Game, Anchorage

    Google Scholar 

  • McKinney MA et al (2011a) Regional contamination versus regional dietary differences: understanding geographic variation in brominated and chlorinated contaminant levels in polar bears. Environ Sci Technol 45:896–902. doi:10.1021/es102781b

    Article  CAS  PubMed  Google Scholar 

  • McKinney MA et al (2011b) Flame retardants and legacy contaminants in polar bears from Alaska, Canada, East Greenland and Svalbard, 2005–2008. Environ Int 37:365–374. doi:10.1016/j.envint.2010.10.008

    Article  CAS  PubMed  Google Scholar 

  • McKinney MA et al (2012) Trophic transfer of contaminants in a changing arctic marine food web: Cumberland Sound, Nunavut, Canada. Environ Sci Technol 46:9914–9922. doi:10.1021/es302761p

    Article  CAS  PubMed  Google Scholar 

  • McMeans BC, Arts MT, Olin JA, Benz GW (2009) Stable-isotope comparisons between embryos and mothers of a placentatrophic shark species. J Fish Biol 75:2464–2474

    Article  CAS  PubMed  Google Scholar 

  • Menni C, Zierer J, Valdes AM, Spector TD (2017) Mixing omics: combining genetics and metabolomics to study rheumatic diseases. Nat Rev Rheumatol 13:174–181. doi:10.1038/nrrheum.2017.5

    Article  CAS  PubMed  Google Scholar 

  • Morris AD, Letcher RJ, Dyck MG, Chandramouli B, Cosgrove JR (2016) Investigating relationships between contaminant and metabolomics profiles in polar bears (Ursus maritimus) from the Hudson Bay Region of Canada. Society of Environmental Toxicology and Chemistry, 7th World Congress, Orlando, FL, USA

  • Muir DC et al (2006) Brominated flame retardants in polar bears (Ursus maritimus) from Alaska, the Canadian Arctic, East Greenland, and Svalbard. Environ Sci Technol 40:449–455

    Article  CAS  PubMed  Google Scholar 

  • Muir DCG et al (2013) Occurrence and trends in the biological environment. In: Muir DCG, Kurt-Karakus P, Stow J (eds) Canadian arctic contaminants assessment report (CACAR) on persistent organic pollutants—2013. Aboriginal Affairs and Northern Development Canada, Ottawa, pp 273–422

    Google Scholar 

  • Newsholme P, Lima MMR, Procopio J, Pithon-Curi TC, Doi SQ, Bazotte RB, Curi R (2003) Glutamine and glutamate as vital metabolites. Braz J Med Biol Res 36:153–163

    Article  CAS  PubMed  Google Scholar 

  • Niemuth JN, Stoskopf MK (2014) Hepatic metabolomic investigation of the North American black bear (Ursus americanus) using 1H-NMR spectroscopy. Wildl Biol Pract 10:14–23. doi:10.2461/wbp.2014.10.3

    Article  Google Scholar 

  • O’Kane AA, Chevallier OP, Graham SF, Elliot CT, Mooney MH (2013) Metabolomic profiling of in vivo plasma responses to dioxin-associated dietary contaminant exposure in rats: implications for identification of sources of animal and human exposure. Environ Sci Technol 47:5409–5418. doi:10.1021/es305345u

    Article  PubMed  Google Scholar 

  • Paapstel K, Kals J, Eha J, Tootsi K, Ottas A, Piir A, Zilmer M (2016) Metabolomic profiles of lipid metabolism, arterial stiffness and hemodynamics in male coronary artery disease patients. IJC Metab Endocr 11:13–18. doi:10.1016/j.ijcme.2016.05.001

    Article  Google Scholar 

  • Rounick JS, Winterbourn MJ (1986) Stable carbon isotopes and carbon flow in ecosystems. Bioscience 36:171–177. doi:10.2307/1310304

    Article  CAS  Google Scholar 

  • Sadler T, Kuster C, von Elert E (2014) Seasonal dynamics of chemotypes in a freshwater phytoplankton community—a metabolomic approach. Harmful Algae 39:102–111

    Article  CAS  Google Scholar 

  • Samuelsson LM, Bjorlenius B, Forlin L, Larsson DGJ (2011) Reproducible 1H NMR-based metabolomic responses in fish exposed to different sewage effluents in two separate studies. Environ Sci Technol 45:1703–1710. doi:10.1021/es104111x

    Article  CAS  PubMed  Google Scholar 

  • Schmitz G, Ecker J (2008) The opposing effects of n-3 and n-6 fatty acids. Prog Lipid Res 47:147–155. doi:10.1016/j.plipres.2007.12.004

    Article  CAS  PubMed  Google Scholar 

  • Schrimpe-Rutledge AC, Codreanu SG, Sherrod SD, McLean JA (2016) Untargeted metabolomics strategies-challenges and emerging directions. J Am Soc Mass Spectrom 27:1897–1905. doi:10.1007/s13361-016-1469-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skelton DM, Ekman DR, Martinovic-Weigelt D, Ankley GT, Villeneuve DL, Teng Q, Collette TW (2013) Metabolomics for in situ environmental monitoring of surface waters impacted by contaminants from both point and nonpoint sources. Environ Sci Technol 48:2395–2403. doi:10.1021/es404021f

    Google Scholar 

  • Sponheimer M et al (2006) Turnover of stable carbon isotopes in the muscle, liver, and breath CO2 of alpacas (Lama pacos). Rapid Commun Mass Spectrom 20:1395–1399

    Article  CAS  PubMed  Google Scholar 

  • Stillwell W, Wassall SR (2003) Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids 126:1–27

    Article  CAS  PubMed  Google Scholar 

  • Størseth TR, Bytingsvik J, Standal IB, Hansen BH, Jenssen BM (2009) Gender differences in the metabolic profiles of blood plasma from polar bear (Ursus maritimus) analyzed by 1H-NMR metabolomics. In: 5th international conference of the metabolomics society, Edmonton

  • Stryer L (1995) Biochemistry, 4th edn. Freeman & Company, W.H

    Google Scholar 

  • Thiemann GW, Iverson SJ, Stirling I (2006) Seasonal, sexual and anatomical variability in the adipose tissue of polar bears (Ursus maritimus). J Zool 269:65–76

    Article  Google Scholar 

  • Thiemann GW, Iverson SJ, Stirling I (2008) Polar bear diets and arctic marine food webs: insights from fatty acid analysis. Ecol Monogr 78:591–613. doi:10.1890/07-1050.1

    Article  Google Scholar 

  • Tieszen LL, Boutton TW, Tesdahl KG, Slade NA (1983) Fractionation and turnover of stable carbon isotopes in animal tissues: implications for δ13C analysis of diet. Oecologia 57:32–37

    Article  CAS  PubMed  Google Scholar 

  • van Ginneken V et al (2007) Metabolomics (liver and blood profiling) in a mouse model in response to fasting: a study of hepatic steatosis. Biochim Biophys Acta 1771:1263–1270. doi:10.1016/j.bbalip.2007.07.007

    Article  PubMed  Google Scholar 

  • Waxman DJ, Celenza JL (2003) Sexual dimorphism of hepatic gene expression: novel biological role of KRAB zinc finger repressors revealed. Genes Dev 17:2607–2613. doi:10.1101/gad.1154603

    Article  CAS  PubMed  Google Scholar 

  • Welch AJ, Bedoya-Reina OC, Carretero-Paulet L, Miller W, Rode KD, Lindqvist C (2014) Polar bears exhibit genome-wide signatures of bioenergetic adaptation to life in the arctic environment. Genome Biol Evol 6:433–450. doi:10.1093/gbe/evu025

    Article  PubMed  PubMed Central  Google Scholar 

  • Xia J, Wishart DS (2011) Web-based inference of biological patterns, functions and pathways from metabolomic data using MetaboAnalyst. Nat Protoc 6:743–760. doi:10.1038/nprot.2011.319

    Article  CAS  PubMed  Google Scholar 

  • Xie J, Sinelnikov I, Han B, Wishart DS (2015) MetaboAnalyst 3.0—making metabolomics more meaningful. Nucleic Acids Res 43:W251–W257

    Article  Google Scholar 

  • Yates FE, Herbst AL, Urquhart J (1958) Sex difference in rate of ring A reduction of delta 4-3-keto-steroids in vitro by rat liver. Endocrinology 63:887–902. doi:10.1210/endo-63-6-887

    Article  CAS  PubMed  Google Scholar 

  • Zhang D et al (2015) Changes in the milk metabolome of the giant panda (Ailuropoda melanoleuca) with time after birth—three phases in early lactation and progressive individual differences. PLoS ONE 10:e0143417. doi:10.1371/journal.pone.0143417

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank our indigenous coworkers in the North who carried out the traditional polar bear hunts and allowed samples to be collected from these animals. We also acknowledge our coworkers and technicians at Environment and Climate Change Canada (National Wildlife Research Centre, Letcher Laboratory), SGS AXYS, and with the Government of Nunavut. Susie Huang and Heather Butler (SGS AXYS) provided valuable feedback on the manuscript and statistical treatment of the data. We also thank the Northern Contaminants Programme [Indigenous and Northern Affairs Canada (INAC), Grant No. INAC-NCP-M05] for funding and supporting this project.

Author information

Authors and Affiliations

  1. Ecotoxicology and Wildlife Health Division, National Wildlife Research Centre, Environment and Climate Change Canada, Ottawa, ON, Canada

    A. D. Morris & R. J. Letcher

  2. Department of Chemistry, Carleton University, Ottawa, ON, Canada

    A. D. Morris & R. J. Letcher

  3. Department of Environment, Government of Nunavut, Igloolik, NU, Canada

    M. Dyck

  4. AXYS Analytical Services, Sidney, BC, Canada

    B. Chandramouli & J. Cosgrove

  5. Great Lakes Institute for Environmental Research, University of Windsor, Windsor, ON, Canada

    A. T. Fisk

Authors
  1. A. D. Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. J. Letcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Dyck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. Chandramouli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. T. Fisk
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. Cosgrove
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. D. Morris.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 1981 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morris, A.D., Letcher, R.J., Dyck, M. et al. Multivariate statistical analysis of metabolomics profiles in tissues of polar bears (Ursus maritimus) from the Southern and Western Hudson Bay subpopulations. Polar Biol 41, 433–449 (2018). https://doi.org/10.1007/s00300-017-2200-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00300-017-2200-6

Keywords

Search

Navigation