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Dietary pattern associated with selenoprotein P and MRI-derived body fat volumes, liver signal intensity, and metabolic disorders

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Abstract

Purpose

The association of complex dietary patterns with circulating selenoprotein P (SELENOP) levels in humans is unknown. In a general population sample, we aimed to identify a dietary pattern explaining inter-individual variation in circulating SELENOP concentrations and to study this pattern in relation to prevalent diabetes, metabolic syndrome (MetS), MRI-determined total volumes of visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, and liver signal intensity/fatty liver disease.

Methods

In this cross-sectional study, serum SELENOP levels were measured in 853 individuals. In a subsample of 553 participants, whole-body MRI was performed to assess body fat distribution and liver fat. Dietary intake was assessed by a self-administered food frequency questionnaire and the dietary pattern identified using reduced-rank regression (RRR). Multivariable linear and logistic regressions were used to investigate associations between dietary pattern score and metabolic traits.

Results

Characterized by high intake of fruit, vegetables and antioxidant beverages, the RRR-derived dietary pattern displayed inverse associations with VAT, SAT, MetS, and prevalent diabetes in multivariable-adjusted restricted cubic splines. Each unit increase in dietary pattern score was associated with 31% higher SELENOP levels, 12% lower VAT (95% CI: − 19%; − 5%), 13% (95% CI: − 20%; − 6%) lower SAT values and 46% (95% CI: 27%; 60%) and 53% (95% CI: 22%; 72%) lower odds of having MetS or diabetes, respectively. No meaningful relations were observed between the dietary pattern and liver traits.

Conclusions

Our observations propose diet-related regulation in SELENOP levels and that the identified dietary pattern is inversely related to VAT, SAT, MetS, and prevalent diabetes.

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References

  1. Burk RF, Hill KE (2005) Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis. Annu Rev Nutr 25:215–235. https://doi.org/10.1146/annurev.nutr.24.012003.132120

    Article  CAS  PubMed  Google Scholar 

  2. Misu H, Takamura T, Takayama H, Hayashi H, Matsuzawa-Nagata N, Kurita S, Ishikura K, Ando H, Takeshita Y, Ota T, Sakurai M, Yamashita T, Mizukoshi E, Honda M, Miyamoto K, Kubota T, Kubota N, Kadowaki T, Kim HJ, Lee IK, Minokoshi Y, Saito Y, Takahashi K, Yamada Y, Takakura N, Kaneko S (2010) A liver-derived secretory protein, selenoprotein P, causes insulin resistance. Cell Metab 12(5):483–495. https://doi.org/10.1016/j.cmet.2010.09.015

    Article  CAS  PubMed  Google Scholar 

  3. di Giuseppe R, Koch M, Schlesinger S, Borggrefe J, Both M, Müller H, Kassubek J, Jacobs G, Nöthlings U, Lieb W (2017) Circulating selenoprotein P levels in relation to MRI-derived body fat volumes, liver fat content, and metabolic disorders. Obesity. https://doi.org/10.1002/oby.21841 (press)

    Article  PubMed  Google Scholar 

  4. Ko BJ, Kim SM, Park KH, Park HS, Mantzoros CS (2014) Levels of circulating selenoprotein P, fibroblast growth factor (FGF) 21 and FGF23 in relation to the metabolic syndrome in young children. Int J Obes (Lond) 38(12):1497–1502. https://doi.org/10.1038/ijo.2014.45

    Article  CAS  Google Scholar 

  5. Choi HY, Hwang SY, Lee CH, Hong HC, Yang SJ, Yoo HJ, Seo JA, Kim SG, Kim NH, Baik SH, Choi DS, Choi KM (2013) Increased selenoprotein p levels in subjects with visceral obesity and nonalcoholic Fatty liver disease. Diabetes Metab J 37(1):63–71. https://doi.org/10.4093/dmj.2013.37.1.63

    Article  PubMed  PubMed Central  Google Scholar 

  6. Persson-Moschos M, Alfthan G, Akesson B (1998) Plasma selenoprotein P levels of healthy males in different selenium status after oral supplementation with different forms of selenium. Eur J Clin Nutr 52(5):363–367

    Article  CAS  PubMed  Google Scholar 

  7. Hill KE, Xia Y, Akesson B, Boeglin ME, Burk RF (1996) Selenoprotein P concentration in plasma is an index of selenium status in selenium-deficient and selenium-supplemented Chinese subjects. J Nutr 126(1):138–145

    Article  CAS  PubMed  Google Scholar 

  8. Duffield AJ, Thomson CD, Hill KE, Williams S (1999) An estimation of selenium requirements for New Zealanders. Am J Clin Nutr 70(5):896–903

    Article  CAS  PubMed  Google Scholar 

  9. Outzen M, Tjonneland A, Larsen EH, Andersen KK, Christensen J, Overvad K, Olsen A (2015) The effect on selenium concentrations of a randomized intervention with fish and mussels in a population with relatively low habitual dietary selenium intake. Nutrients 7(1):608–624. https://doi.org/10.3390/nu7010608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hu FB (2002) Dietary pattern analysis: a new direction in nutritional epidemiology. Curr Opin Lipidol 13(1):3–9

    Article  CAS  PubMed  Google Scholar 

  11. Hoffmann K, Schulze MB, Schienkiewitz A, Nothlings U, Boeing H (2004) Application of a new statistical method to derive dietary patterns in nutritional epidemiology. Am J Epidemiol 159(10):935–944

    Article  PubMed  Google Scholar 

  12. Nothlings U, Krawczak M (2012) PopGen. A population-based biobank with prospective follow-up of a control group. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 55(6–7):831–835. https://doi.org/10.1007/s00103-012-1487-2

    Article  CAS  PubMed  Google Scholar 

  13. Koch M, Borggrefe J, Barbaresko J, Groth G, Jacobs G, Siegert S, Lieb W, Muller MJ, Bosy-Westphal A, Heller M, Nothlings U (2014) Dietary patterns associated with magnetic resonance imaging-determined liver fat content in a general population study. Am J Clin Nutr 99(2):369–377. https://doi.org/10.3945/ajcn.113.070219

    Article  CAS  PubMed  Google Scholar 

  14. Nothlings U, Hoffmann K, Bergmann MM, Boeing H (2007) Fitting portion sizes in a self-administered food frequency questionnaire. J Nutr 137(12):2781–2786

    Article  PubMed  Google Scholar 

  15. Barbaresko J, Siegert S, Koch M, Aits I, Lieb W, Nikolaus S, Laudes M, Jacobs G, Nothlings U (2014) Comparison of two exploratory dietary patterns in association with the metabolic syndrome in a Northern German population. Br J Nutr 112(8):1364–1372. https://doi.org/10.1017/S0007114514002098

    Article  CAS  PubMed  Google Scholar 

  16. Kroger J, Ferrari P, Jenab M, Bamia C, Touvier M, Bueno-de-Mesquita HB, Fahey MT, Benetou V, Schulz M, Wirfalt E, Boeing H, Hoffmann K, Schulze MB, Orfanos P, Oikonomou E, Huybrechts I, Rohrmann S, Pischon T, Manjer J, Agren A, Navarro C, Jakszyn P, Boutron-Ruault MC, Niravong M, Khaw KT, Crowe F, Ocke MC, van der Schouw YT, Mattiello A, Bellegotti M, Engeset D, Hjartaker A, Egeberg R, Overvad K, Riboli E, Bingham S, Slimani N (2009) Specific food group combinations explaining the variation in intakes of nutrients and other important food components in the European Prospective Investigation into Cancer and Nutrition: an application of the reduced rank regression method. Eur J Clin Nutr 63(Suppl 4):S263–S274. https://doi.org/10.1038/ejcn.2009.85

    Article  PubMed  Google Scholar 

  17. Colditz GA, Willett WC (1991) Epidemiologic approaches to the study of diet and cancer. In: AlfSlater RB, Kritchevsky D, AlfSlater RB, Kritchevsky D (eds) Cancer and nutrition se epidemiologic approaches to the study of diet and cancer, 1st edn. Springer, New York, pp 58–60

    Google Scholar 

  18. Karita K, Sasaki S, Ishihara J, Tsugane S (2003) Validity of a self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC Study to assess selenium intake: comparison with dietary records and blood levels. J Epidemiol 13(1 Suppl):S92-97

    Google Scholar 

  19. Hurst R, Armah CN, Dainty JR, Hart DJ, Teucher B, Goldson AJ, Broadley MR, Motley AK, Fairweather-Tait SJ (2010) Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 91(4):923–931. https://doi.org/10.3945/ajcn.2009.28169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Stoffaneller R, Morse NL (2015) A review of dietary selenium intake and selenium status in Europe and the Middle East. Nutrients 7(3):1494–1537. https://doi.org/10.3390/nu7031494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ainsworth BE, Haskell WL, Herrmann SD, Meckes N, Bassett DR Jr, Tudor-Locke C, Greer JL, Vezina J, Whitt-Glover MC, Leon AS (2011) Compendium of physical activities: a second update of codes and MET values. Med Sci Sports Exerc 43(8):1575–1581. https://doi.org/10.1249/MSS.0b013e31821ece12

    Article  PubMed  Google Scholar 

  22. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120(16):1640–1645. https://doi.org/10.1161/CIRCULATIONAHA.109.192644

    Article  CAS  PubMed  Google Scholar 

  23. Fischer K, Moewes D, Koch M, Muller HP, Jacobs G, Kassubek J, Lieb W, Nothlings U (2015) MRI-determined total volumes of visceral and subcutaneous abdominal and trunk adipose tissue are differentially and sex-dependently associated with patterns of estimated usual nutrient intake in a northern German population. Am J Clin Nutr 101(4):794–807. https://doi.org/10.3945/ajcn.114.101626

    Article  CAS  PubMed  Google Scholar 

  24. Muller HP, Raudies F, Unrath A, Neumann H, Ludolph AC, Kassubek J (2011) Quantification of human body fat tissue percentage by MRI. NMR Biomed 24(1):17–24. https://doi.org/10.1002/nbm.1549

    Article  PubMed  Google Scholar 

  25. Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288(2):E462-468. https://doi.org/10.1152/ajpendo.00064.2004

    Article  CAS  Google Scholar 

  26. Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65 (4 Suppl):1220S–1228S. (Discussion 1229S-1231S)

    Article  CAS  PubMed  Google Scholar 

  27. Hu FB, Rimm E, Smith-Warner SA, Feskanich D, Stampfer MJ, Ascherio A, Sampson L, Willett WC (1999) Reproducibility and validity of dietary patterns assessed with a food-frequency questionnaire. Am J Clin Nutr 69(2):243–249

    Article  CAS  PubMed  Google Scholar 

  28. McNaughton SA, Mishra GD, Brunner EJ (2008) Dietary patterns, insulin resistance, and incidence of type 2 diabetes in the Whitehall II Study. Diabetes Care 31(7):1343–1348. https://doi.org/10.2337/dc07-1946

    Article  PubMed  PubMed Central  Google Scholar 

  29. Desquilbet L, Mariotti F (2010) Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 29(9):1037–1057. https://doi.org/10.1002/sim.3841

    Article  PubMed  Google Scholar 

  30. Xia Y, Hill KE, Byrne DW, Xu J, Burk RF (2005) Effectiveness of selenium supplements in a low-selenium area of China. Am J Clin Nutr 81(4):829–834

    Article  CAS  PubMed  Google Scholar 

  31. Meplan C, Crosley LK, Nicol F, Beckett GJ, Howie AF, Hill KE, Horgan G, Mathers JC, Arthur JR, Hesketh JE (2007) Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study). FASEB J 21(12):3063–3074. https://doi.org/10.1096/fj.07-8166com

    Article  CAS  PubMed  Google Scholar 

  32. Hagmar L, Persson-Moschos M, Akesson B, Schutz A (1998) Plasma levels of selenium, selenoprotein P and glutathione peroxidase and their correlations to fish intake and serum levels of thyrotropin and thyroid hormones: a study on Latvian fish consumers. Eur J Clin Nutr 52(11):796–800

    Article  CAS  PubMed  Google Scholar 

  33. Huang W, Akesson B, Svensson BG, Schutz A, Burk RF, Skerfving S (1995) Selenoprotein P and glutathione peroxidase (EC 1.11.1.9) in plasma as indices of selenium status in relation to the intake of fish. Br J Nutr 73(3):455–461

    Article  CAS  PubMed  Google Scholar 

  34. Rasmussen LB, Hollenbach B, Laurberg P, Carle A, Hog A, Jorgensen T, Vejbjerg P, Ovesen L, Schomburg L (2009) Serum selenium and selenoprotein P status in adult Danes—8-year followup. J Trace Elem Med Biol 23(4):265–271. https://doi.org/10.1016/j.jtemb.2009.03.009

    Article  CAS  PubMed  Google Scholar 

  35. Combs GF Jr (2015) Biomarkers of selenium status. Nutrients 7(4):2209–2236. https://doi.org/10.3390/nu7042209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Daniels LA (1996) Selenium metabolism and bioavailability. Biol Trace Elem Res 54(3):185–199. https://doi.org/10.1007/BF02784430

    Article  CAS  PubMed  Google Scholar 

  37. Sobiecki JG (2017) Vegetarianism and colorectal cancer risk in a low-selenium environment: effect modification by selenium status? A possible factor contributing to the null results in British vegetarians. Eur J Nutr 56(5):1819–1832. https://doi.org/10.1007/s00394-016-1364-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Renko K, Martitz J, Hybsier S, Heynisch B, Voss L, Everley RA, Gygi SP, Stoedter M, Wisniewska M, Kohrle J, Gladyshev VN, Schomburg L (2017) Aminoglycoside-driven biosynthesis of selenium-deficient Selenoprotein P. Sci Rep 7(1):4391. https://doi.org/10.1038/s41598-017-04586-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Renko K, Hofmann PJ, Stoedter M, Hollenbach B, Behrends T, Kohrle J, Schweizer U, Schomburg L (2009) Down-regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice. FASEB J 23(6):1758–1765. https://doi.org/10.1096/fj.08-119370

    Article  CAS  PubMed  Google Scholar 

  40. Hesse-Bahr K, Dreher I, Kohrle J (2000) The influence of the cytokines Il-1beta and INFgamma on the expression of selenoproteins in the human hepatocarcinoma cell line HepG2. Biofactors 11(1–2):83–85

    Article  CAS  PubMed  Google Scholar 

  41. Haug A, Graham RD, Christophersen OA, Lyons GH (2007) How to use the world’s scarce selenium resources efficiently to increase the selenium concentration in food. Microb Ecol Health Dis 19(4):209–228. https://doi.org/10.1080/08910600701698986

    Article  CAS  PubMed  Google Scholar 

  42. Ogawa-Wong AN, Berry MJ, Seale LA (2016) Selenium and metabolic disorders: an emphasis on type 2. Diabetes Risk Nutr 8(2):80. https://doi.org/10.3390/nu8020080

    Article  CAS  Google Scholar 

  43. Joseph J (2013) Selenium and cardiometabolic health: inconclusive yet intriguing evidence. Am J Med Sci 346(3):216–220. https://doi.org/10.1097/MAJ.0b013e3182638716

    Article  PubMed  PubMed Central  Google Scholar 

  44. Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, Cappuccio FP, Ceriello A, Reid ME (2007) Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med 147(4):217–223

    Article  PubMed  Google Scholar 

  45. Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, Parnes HL, Minasian LM, Gaziano JM, Hartline JA, Parsons JK, Bearden JD, 3rd, Crawford ED, Goodman GE, Claudio J, Winquist E, Cook ED, Karp DD, Walther P, Lieber MM, Kristal AR, Darke AK, Arnold KB, Ganz PA, Santella RM, Albanes D, Taylor PR, Probstfield JL, Jagpal TJ, Crowley JJ, Meyskens FL Jr, Baker LH, Coltman CA, Jr (2009) Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301(1):39–51. https://doi.org/10.1001/jama.2008.864

    Article  CAS  PubMed  Google Scholar 

  46. Stranges S, Navas-Acien A, Rayman MP, Guallar E (2010) Selenium status and cardiometabolic health: state of the evidence. Nutr Metab Cardiovasc Dis 20(10):754–760. https://doi.org/10.1016/j.numecd.2010.10.001

    Article  CAS  PubMed  Google Scholar 

  47. Reszka E, Jablonska E, Gromadzinska J, Wasowicz W (2012) Relevance of selenoprotein transcripts for selenium status in humans. Genes Nutr 7(2):127–137. https://doi.org/10.1007/s12263-011-0246-6

    Article  CAS  PubMed  Google Scholar 

  48. Carnauba RA, Chaves DF, Baptistella AB, Paschoal V, Naves A, Buehler AM (2016) Association between high consumption of phytochemical-rich foods and anthropometric measures: a systematic review. Int J Food Sci Nutr 1–9. https://doi.org/10.1080/09637486.2016.1229761

  49. Rodriguez-Monforte M, Sanchez E, Barrio F, Costa B, Flores-Mateo G (2016) Metabolic syndrome and dietary patterns: a systematic review and meta-analysis of observational studies. Eur J Nutr. https://doi.org/10.1007/s00394-016-1305-y

    Article  PubMed  Google Scholar 

  50. Gamboa-Gomez CI, Rocha-Guzman NE, Gallegos-Infante JA, Moreno-Jimenez MR, Vazquez-Cabral BD, Gonzalez-Laredo RF (2015) Plants with potential use on obesity and its complications. EXCLI J 14:809–831. https://doi.org/10.17179/excli2015-186

    Article  PubMed  PubMed Central  Google Scholar 

  51. Groenwold RH, Klungel OH, Altman DG, van der Graaf Y, Hoes AW, Moons KG (2013) Adjustment for continuous confounders: an example of how to prevent residual confounding. CMAJ 185(5):401–406. https://doi.org/10.1503/cmaj.120592

    Article  PubMed  PubMed Central  Google Scholar 

  52. Altinova AE, Iyidir OT, Ozkan C, Ors D, Ozturk M, Gulbahar O, Bozkurt N, Toruner FB, Akturk M, Cakir N, Arslan M (2015) Selenoprotein P is not elevated in gestational diabetes mellitus. Gynecol Endocrinol 31(11):874–876. https://doi.org/10.3109/09513590.2015.1103220

    Article  CAS  PubMed  Google Scholar 

  53. Chen M, Liu B, Wilkinson D, Hutchison AT, Thompson CH, Wittert GA, Heilbronn LK (2017) Selenoprotein P is elevated in individuals with obesity, but is not independently associated with insulin resistance. Obes Res Clin Pract 11(2):227–232. https://doi.org/10.1016/j.orcp.2016.07.004

    Article  PubMed  Google Scholar 

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Acknowledgements

R.d.G. is supported by the Deutsche Forschungsgemeinschaft Excellence Cluster “Inflammation at Interfaces” (Grant EXC306/2). Koch M. is recipient of a Postdoctoral Research Fellowship from the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft). The PopGen 2.0 network is supported by the German Federal Ministry of Education and Research (Grant 01EY1103).

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Authors and Affiliations

  1. Institute of Epidemiology, Christian-Albrechts University of Kiel, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Niemannsweg 11, 24105, Kiel, Germany

    Romina di Giuseppe, Sandra Plachta-Danielzik, Manja Koch, Gunnar Jacobs & Wolfgang Lieb

  2. Biobank PopGen, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Gunnar Jacobs & Wolfgang Lieb

  3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Manja Koch

  4. Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany

    Ute Nöthlings

  5. Institute for Biometrics and Epidemiology, Junior Research Group Systematic Reviews, German Diabetes Center, Düsseldorf, Germany

    Sabrina Schlesinger

  6. Institute of Radiological Diagnostics Köln, Cologne, Germany

    Jan Borggrefe

  7. Department of Diagnostic Radiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    Marcus Both

  8. Department of Neurology, University of Ulm, Ulm, Germany

    Hans-Peter Müller & Jan Kassubek

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  1. Romina di Giuseppe
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Correspondence to Romina di Giuseppe.

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di Giuseppe, R., Plachta-Danielzik, S., Koch, M. et al. Dietary pattern associated with selenoprotein P and MRI-derived body fat volumes, liver signal intensity, and metabolic disorders. Eur J Nutr 58, 1067–1079 (2019). https://doi.org/10.1007/s00394-018-1624-2

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