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Measuring short-term liver metabolism non-invasively: postprandial and post-exercise 1H and 31P MR spectroscopy

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Abstract

Object

The objective of this study was to determine the effects of a standardized fat rich meal and subsequent exercise on liver fat content by 1H MRS and on liver adenosine triphosphate (ATP) content by 31P MRS in healthy subjects.

Materials and methods

Hepatic 1H and proton decoupled 31P MRS were performed on nine healthy subjects on a clinical 3.0 T MR imager three times during a day: after (1) an overnight fast, (2) a following standardized fat rich meal and (3) a subsequent exercise session. Blood parameters were followed during the day to serve as a reference to MRS.

Results

Liver fat content increased gradually over the day (p = 0.0001) with an overall increase of 30 %. Also γ-NTP changed significantly over the day (p = 0.005). γ-NTP/tP decreased by 9 % (p = 0.019, post hoc) from the postprandial to the post-exercise state.

Conclusion

Our study shows that in vivo MRS can depict short lived physiological changes; entering of fat into liver cells and consumption of ATP during exercise can be measured non-invasively in healthy subjects. The physiological state may have an impact on fat and energy metabolite levels. Hepatic 1H and 31P MRS studies should be performed under standardized conditions.

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Abbreviations

ANOVA:

Analysis of variance

ASH:

Alcoholic steatohepatitis

ATP:

Adenosine triphosphate

FFA:

Free fatty acids

FID:

Free induction decay

GPC:

Glycerophosphocholine

GPE:

Glycerophosphoethanolamine

GTP:

Guanosine triphosphate

HCT:

Hematocrit

HDL-C:

High-density lipoprotein cholesterol

IHCL:

Intra hepatocellular lipids

ISIS:

Image selective in vivo spectroscopy

LDL-C:

Low-density lipoprotein cholesterol

MCH:

Mean corpuscular hemoglobin

MCHC:

Mean corpuscular hemoglobin concentration

MRS:

Magnetic resonance spectroscopy

NADPH:

Nicotinamide adenine dinucleotide phosphate

NTP:

Nucleoside triphosphate

PC:

Phosphocholine

PDE:

Phosphodiesters

PE:

Phosphoethanolamine

PEP:

Phosphoenolpyruvate

Pi:

Inorganic phosphates

PME:

Phosphomonoesters

PtdC:

Phosphatidylcholine

RDW:

Red blood cell distribution width

SNR:

Signal-to-noise ratio

T2DM:

Type 2 diabetes mellitus

TG:

Triglycerides

tP:

Total phosphorus

WBC:

White blood cells

References

  1. Lundbom J, Hakkarainen A, Söderlund S, Westerbacka J, Lundbom N, Taskinen M (2011) Long-TE 1H MRS suggests that liver fat is more saturated than subcutaneous and visceral fat. NMR Biomed 24:238–245

    Article  PubMed  Google Scholar 

  2. Khan SA, Cox IJ, Hamilton G, Thomas HC, Taylor-Robinson SD (2005) In vivo and in vitro nuclear magnetic resonance spectroscopy as a tool for investigating hepatobiliary disease: a review of 1H and 31P MRS applications. Liver Int 25:273–281

    Article  CAS  PubMed  Google Scholar 

  3. Gallis J, Delmas-Beauvieux M, Biran M, Rousse N, Durand T, Canioni P (1991) Is cellular integrity responsible for the partial NMR invisibility of ATP in isolated ischemic rat liver? NMR Biomed 4:279–285

    Article  CAS  PubMed  Google Scholar 

  4. Cortez-Pinto H, Chatham J, Chacko VP, Arnold C, Rashid A, Diehl A (1999) Alterations in liver atp homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA 282:1659–1664

    Article  CAS  PubMed  Google Scholar 

  5. Nair S, Chacko VP, Arnold C, Diehl AM (2003) Hepatic ATP reserve and efficiency of replenishing: comparison between obese and nonobese normal individuals. Am J Gastroenterol 98:466–470

    CAS  PubMed  Google Scholar 

  6. Szendroedi J, Chmelik M, Schmid AI, Nowotny P, Brehm A, Krssak M, Moser E, Roden M (2009) Abnormal hepatic energy homeostasis in type 2 diabetes. Hepatology 50:1079–1086

    Article  CAS  PubMed  Google Scholar 

  7. Dezortova M, Taimr P, Skoch A, Spicak J, Hajek M (2005) Etiology and functional status of liver cirrhosis by 31P MR spectroscopy. World J Gastroenterol 11:6926–6931

    CAS  PubMed  Google Scholar 

  8. Rajanayagam V, Lee RR, Ackerman Z, Bradley WG, Ross BD (1992) Quantitative P-31 MR spectroscopy of the liver in alcoholic cirrhosis. J Magn Reson Imaging 2:183–190

    Article  CAS  PubMed  Google Scholar 

  9. Leij-Halfwerk S, Dagnelie PC, Kappert P, Oudkerk M, Sijens PE (2000) Decreased energy and phosphorylation status in the liver of lung cancer patients with weight loss. J Hepatol 32:887–892

    Article  CAS  PubMed  Google Scholar 

  10. Abdelmalek MF, Lazo M, Horska A, Bonekamp S, Lipkin EW, Balasubramanyam A, Bantle JP, Johnson RJ, Diehl AM, Clark JM, and the Fatty Liver Subgroup of the Look AHEAD Research Group (2012) Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes. Hepatology 56:952–960

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Jalan R, Sargentoni J, Coutts GA, Bell JD, Rolles K, Burroughs AK, Taylor Robinson SD (1996) Hepatic phosphorus-31 magnetic resonance spectroscopy in primary biliary cirrhosis and its relation to prognostic models. Gut 39:141–146

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Kiyono K, Shibata A, Sone S, Watanabe T, Oguchi M, Shikama N, Ichijo T, Kiyosawa K, Sodeyama T (1998) Relationship of 31P MR spectroscopy to the histopathological grading of chronic hepatitis and response to therapy. Acta Radiol 39:309–314

    Article  CAS  PubMed  Google Scholar 

  13. van Werven JR, Hoogduin JM, Nederveen AJ, van Vliet AA, Wajs E, Vandenberk P, Stroes ESG, Stoker J (2009) Reproducibility of 3.0 Tesla magnetic resonance spectroscopy for measuring hepatic fat content. J Magn Reson Imaging 30:444–448

    Article  PubMed  Google Scholar 

  14. 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:E462–E468

    Article  CAS  PubMed  Google Scholar 

  15. Yki-Järvinen H (2010) Nutritional modulation of nonalcoholic fatty liver disease and insulin resistance: human data. Curr Opin Clin Nut Metab Care 13(6):709–714

    Article  Google Scholar 

  16. Magkos F (2010) Exercise and fat accumulation in the human liver. Curr Opin Lipidol 21(6):507–517

    Article  CAS  PubMed  Google Scholar 

  17. Boesch C, Egger A, Kreis R, Ith M, Krull I, Nuoffer J, Diem P, Stettler C, Christ ER (2008) ESMRMB 2008 Congress, Valencia, Spain, 2–4 October: abstracts, Saturday. 271. Intrahepatocellular lipids (IHCL) increase during exercise together with serum free fatty acids (FFA) while intramyocellular lipids (IMCL) decrease. Magn Reson Mater Phy Biol Med 21:176

    Google Scholar 

  18. Egger A, Kreis R, Allemann S, Stettler C, Diem P, Buehler T, Boesch C, Christ ER (2013) The effect of aerobic exercise on intrahepatocellular and intramyocellular lipids in healthy subjects. PLoS ONE 8:e70865

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Shuhei N, Soderlund S, Jauhiainen M, Taskinen MR (2010) Effect of HDL composition and particle size on the resistance of HDL to the oxidation. Lipids Health Dis 9:104-511X-9-104

  20. Adiels M, Matikainen N, Westerbacka J, Söderlund S, Larsson T, Olofsson S, Borén J, Taskinen M (2012) Postprandial accumulation of chylomicrons and chylomicron remnants is determined by the clearance capacity. Atherosclerosis 222:222–228

    Article  CAS  PubMed  Google Scholar 

  21. Fox SM 3rd, Naughton JP, Haskell WL (1971) Physical activity and the prevention of coronary heart disease. Ann Clin Res 3:404–432

    PubMed  Google Scholar 

  22. Stefan D, Di Cesare F, Andrasescu A, Popa E, Lazariev A, Vescovo E, Strbak O, Williams S, Starcuk Z, Cabanas M, van Ormondt D, Graveron D (2009) Quantitation of magnetic resonance spectroscopy signals: the jMRUI software package. Meas Sci Technol 20:104035

    Article  Google Scholar 

  23. Vanhamme L, van den Boogaart A, Van Huffel S (1997) Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. J Magn Reson 129:35–43

    Article  CAS  PubMed  Google Scholar 

  24. Provencher SW (2001) Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 14:260–264

    Article  CAS  PubMed  Google Scholar 

  25. Hamilton G, Patel N, Forton DM, Hajnal JV, Taylor-Robinson SD (2003) Prior knowledge for time domain quantification of in vivo brain or liver 31P MR spectra. NMR Biomed 16:168–176

    Article  CAS  PubMed  Google Scholar 

  26. Murphy EJ, Rajagopalan B, Brindle KM, Radda GK (1989) Phospholipid bilayer contribution to 31P NMR spectra in vivo. Magn Reson Med 12:282–289

    Article  CAS  PubMed  Google Scholar 

  27. Schmid AI, Chmelík M, Szendroedi J, Krscaronscaronák M, Brehm A, Moser E, Roden M (2008) Quantitative ATP synthesis in human liver measured by localized 31P spectroscopy using the magnetization transfer experiment. NMR Biomed 21:437–443

    Article  CAS  PubMed  Google Scholar 

  28. Chemelík M, Valkovic L, Wolf P, Bogner W, Gajdosík M, Gruber S, Trauner M, Krebs M, Trattnig S, Krssák M (2013) Human bile phosphatidylcholine contributes to 31P MRS hepatic signal at 2.06 ppm. In: Proceedings of the 21st scientific meeting, international society for magnetic resonance in medicine, Salt Lake City, p 4090

  29. Chmelik M, Povazan M, Krssák M, Gruber S, Tkacov M, Trattnig S, Bogner W (2014) In vivo 31P magnetic resonance spectroscopy of the human liver at 7T: an initial experience. NMR Biomed 27:478–485

    Article  CAS  PubMed  Google Scholar 

  30. Wylezinska M, Cobbold JFL, Fitzpatrick J, McPhail MJW, Crossey MME, Thomas HC, Hajnal JV, Vennart W, Cox IJ, Taylor-Robinson SD (2011) A comparison of single-voxel clinical in vivo hepatic 31P MR spectra acquired at 1.5 and 3.0 Tesla in health and diseased states. NMR Biomed 24:231–237

    Article  CAS  PubMed  Google Scholar 

  31. Laufs A, Livingstone R, Nowotny B, Nowotny P, Wickrath F, Giani G, Bunke J, Roden M, Hwang J (2014) Quantitative liver 31P magnetic resonance spectroscopy at 3T on a clinical scanner. Magn Reson Med 71:1670–1675

    Article  CAS  PubMed  Google Scholar 

  32. Rognstad R (1979) Rate-limiting steps in metabolic pathways. J Biol Chem 254:1875–1878

    CAS  PubMed  Google Scholar 

  33. Khan SA, Cox IJ, Thillainayagam AV, Bansi DS, Thomas HC, Taylor-Robinson SD (2005) Proton and phosphorus-31 nuclear magnetic resonance spectroscopy of human bile in hepatopancreaticobiliary cancer. Eur J Gastroenterol Hepatol 17:733–738

    Article  CAS  PubMed  Google Scholar 

  34. Schulz G (1893) Experimentelle Untersuchungen über das Vorkommen und die diagnostische Bedeutung der Leukocytose. Dtsch Arch Klin Med 51:234–281

    Google Scholar 

  35. Alssema M, Schindhelm RK, Dekker JM, Diamant M, Nijpels G, Teerlink T, Scheffer PG, Kostense PJ, Heine RJ (2008) Determinants of postprandial triglyceride and glucose responses after two consecutive fat-rich or carbohydrate-rich meals in normoglycemic women and in women with type 2 diabetes mellitus: the Hoorn Prandial Study. Metab Clin Exp 57:1262–1269

    Article  CAS  PubMed  Google Scholar 

  36. Parks EJ, Hellerstein MK (2006) Thematic review series: patient-oriented research. Recent advances in liver triacylglycerol and fatty acid metabolism using stable isotope labeling techniques. J Lipid Res 47:1651–1660

    Article  CAS  PubMed  Google Scholar 

  37. van Oostrom AJ, van Dijk H, Verseyden C, Sniderman AD, Cianflone K, Rabelink TJ, Castro Cabezas M (2004) Addition of glucose to an oral fat load reduces postprandial free fatty acids and prevents the postprandial increase in complement component 3. Am J Clin Nutr 79:510–515

    PubMed  Google Scholar 

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Acknowledgments

We are grateful to Helinä Perttunen-Nio for excellent laboratory work and to volunteers for participation. This study was funded by the Waldemar von Frenckells Foundation, the Finnish Diabetes Association, the Orion-Pharmos Foundation, Mary and Georg C. Ehrnrooths foundation and Helsinki University Central Hospital: a special governmental subsidy for health sciences research (TLD8100061 and TLD8100073).

Author information

Authors and Affiliations

  1. Department of Radiology, HUS Medical Imaging Center, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland

    Antti Hakkarainen, Jesper Lundbom, Esa K. Tuominen & Nina Lundbom

  2. Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland

    Marja-Riitta Taskinen

  3. Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland

    Kirsi H. Pietiläinen

  4. Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland

    Kirsi H. Pietiläinen

  5. FIMM, Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

    Kirsi H. Pietiläinen

Authors
  1. Antti Hakkarainen
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  2. Jesper Lundbom
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  4. Marja-Riitta Taskinen
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  5. Kirsi H. Pietiläinen
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  6. Nina Lundbom
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Correspondence to Antti Hakkarainen.

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Hakkarainen, A., Lundbom, J., Tuominen, E.K. et al. Measuring short-term liver metabolism non-invasively: postprandial and post-exercise 1H and 31P MR spectroscopy. Magn Reson Mater Phy 28, 57–66 (2015). https://doi.org/10.1007/s10334-014-0450-7

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  • DOI: https://doi.org/10.1007/s10334-014-0450-7

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