Top

Magnetic Resonance Materials in Physics, Biology and Medicine

Published in:

01-10-2012 | Research Article

Hepatic lipid composition differs between ob/ob and ob/+ control mice as determined by using in vivo localized proton magnetic resonance spectroscopy

Authors: Qiong Ye, Carsten Friedrich Danzer, Alexander Fuchs, Christian Wolfrum, Markus Rudin

Published in: Magnetic Resonance Materials in Physics, Biology and Medicine | Issue 5/2012

Abstract

Object

Hepatic lipid accumulation is associated with nonalcoholic fatty liver disease, and the metabolic syndrome constitutes an increasing medical problem. In vivo proton magnetic resonance spectroscopy (¹H MRS) allows the assessment of hepatic lipid levels noninvasively and also yields information on the fat composition due to its high spectral resolution.

Materials and methods

We applied ¹H MRS at 9.4T to study lipid content and composition in eight leptin-deficient ob/ob mice as a model of obesity and in four lean ob/+ control mice at 24 weeks of age. PRESS sequence was used. For accurate estimation of signal intensity, differences in relaxation behavior of individual signals were accounted for each mouse individually. Also, in order to minimize spectral degrading due to motion artifacts, respiration gating was applied.

Results

Significant differences between ob/ob and ob/+ control mice were found in both lipid content and composition. The mean chain length was found to be significantly longer in ob/ob mice with a higher fraction of monounsaturated lipids.

Conclusion

¹H MRS enables accurate assessment in hepatic lipids in mice, which is attractive for mechanistic studies of altered metabolism given the large number of genetically engineered mouse models available.

Krssak M, Roden M (2004) The role of lipid accumulation in liver and muscle for insulin resistance and type 2 diabetes mellitus in humans. Rev Endocr Metab Disord 5:127–134PubMedCrossRef

Kovacs P, Stumvoll M (2005) Fatty acids and insulin resistance in muscle and liver. Best Pract Res Clin Endocrinol Metab 19:625–635PubMedCrossRef

Anstee QM, Goldin RD (2006) Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol 87:1–16PubMedCrossRef

Craske JD (1993) Separation of instrumental and chemical errors in the analysis of oils by gas-chromatography—a collaborative evaluation. J Am Oil Chem Soc 70:325–334CrossRef

Deman JM (1964) Determination of fatty acid composition of milk fat by dual column temperature programmed gas-liquid chromatography. J Dairy Sci 47:546–547CrossRef

Lindon JC, Holmes E, Nicholson JK (2006) Metabonomics techniques and applications to pharmaceutical research and development. Pharm Res 23:1075–1088PubMedCrossRef

Zancanaro C, Nano R, Marchioro C et al (1994) Magnetic resonance spectroscopy investigations of brown adipose tissue and isolated brown adipocytes. J Lipid Res 35:2191–2199PubMed

Knothe G, Kenar JA (2004) Determination of the fatty acid profile by H-1-NMR spectroscopy. Eur J Lipid Sci Tech 106:88–96CrossRef

Miyake Y, Yokomizo K, Matsuzaki N (1998) Determination of unsaturated fatty acid composition by high-resolution nuclear magnetic resonance spectroscopy. J Am Oil Chem Soc 75:1091–1094

10.

Yeung DKW, Lam SL, Griffith JF et al (2008) Analysis of bone marrow fatty acid composition using high-resolution proton NMR spectroscopy. Chem Phys Lipids 151:103–109PubMedCrossRef

11.

Guillen MD, Ruiz A (2003) H-1 nuclear magnetic resonance as a fast tool for determining the composition of acyl chains in acylglycerol mixtures. Eur J Lipid Sci Tech 105:502–507CrossRef

12.

Ruberg FL, Viereck J, Phinikaridou A et al (2006) Identification of cholesteryl esters in human carotid atherosclerosis by ex vivo image-guided proton MRS. J Lipid Res 47:310–317PubMedCrossRef

13.

Ren JM, Dimitrov I, Sherry AD et al (2008) Composition of adipose tissue and marrow fat in humans by H-1 NMR at 7 Tesla. J Lipid Res 49:2055–2062PubMedCrossRef

14.

Hwang JH, Bluml S, Leaf A et al (2003) In vivo characterization of fatty acids in human adipose tissue using natural abundance H-1 clecoupled C-13 MRS at 1.5 T: clinical applications to dietary therapy. NMR Biomed 16:160–167PubMedCrossRef

15.

Lunati E, Farace P, Nicolato E et al (2001) Polyunsaturated fatty acids mapping by (1)H MR-chemical shift imaging. Magn Reson Med 46:879–883PubMedCrossRef

16.

Walling BE, Munasinghe J, Berrigan D et al (2007) Intra-abdominal fat burden discriminated in vivo using proton magnetic resonance spectroscopy. Obesity (Silver Spring) 15:69–77CrossRef

17.

Lunati E, Marzola P, Nicolato E et al (1999) In vivo quantitative lipidic map of brown adipose tissue by chemical shift imaging at 4.7 tesla. J Lipid Res 40:1395–1400PubMed

18.

Strobel K, van den Hoff J, Pietzsch J (2008) Localized proton magnetic resonance spectroscopy of lipids in adipose tissue at high spatial resolution in mice in vivo. J Lipid Res 49:473–480PubMedCrossRef

19.

Lundbom J, Hakkarainen A, Soderlund S et al (2011) Long-TE (1)H MRS suggests that liver fat is more saturated than subcutaneous and visceral fat. NMR Biomed 24:238–245PubMedCrossRef

20.

Bollard ME, Garrod S, Holmes E et al (2000) High-resolution (1)H and (1)H–(13)C magic angle spinning NMR spectroscopy of rat liver. Magn Reson Med 44:201–207PubMedCrossRef

21.

Corbin IR, Furth EE, Pickup S et al (2009) In vivo assessment of hepatic triglycerides in murine non-alcoholic fatty liver disease using magnetic resonance spectroscopy. Bba-Mol Cell Biol L 1791:757–763CrossRef

22.

Calderan L, Marzola P, Nicolato E et al (2006) In vivo phenotyping of the ob/ob mouse by magnetic resonance imaging and 1H-magnetic resonance spectroscopy. Obesity (Silver Spring) 14:405–414CrossRef

23.

Griffitts J, Tesiram Y, Reid GE et al (2009) In vivo MRS assessment of altered fatty acyl unsaturation in liver tumor formation of a TGF alpha/c-myc transgenic mouse model. J Lipid Res 50:611–622PubMedCrossRef

24.

Garbow JR, Lin X, Sakata N et al (2004) In vivo MRS measurement of liver lipid levels in mice. J Lipid Res 45:1364–1371PubMedCrossRef

25.

Dimitrov IE, Douglas D, Ren J et al (2011) In vivo determination of human breast fat composition by (1) H magnetic resonance spectroscopy at 7 T. Magn Reson Med 67:20–26PubMedCrossRef

26.

Mosconi E, Fontanella M, Sima DM et al (2011) Investigation of adipose tissues in Zucker rats using in vivo and ex vivo magnetic resonance spectroscopy. J Lipid Res 52:330–336PubMedCrossRef

27.

Lindstrom P (2007) The physiology of obese-hyperglycemic mice [ob/ob mice]. Sci World J 7:666–685CrossRef

28.

Menahan LA (1983) Age-related changes in lipid and carbohydrate metabolism of the genetically obese mouse. Metabolism 32:172–178PubMedCrossRef

29.

Cheng Y, Zhang J, Shang J et al (2009) Prevention of free fatty acid-induced hepatic lipotoxicity in HepG2 cells by magnesium isoglycyrrhizinate in vitro. Pharmacology 84:183–190PubMedCrossRef

30.

Duncan JG (2008) Lipotoxicity: what is the fate of fatty acids? J Lipid Res 49:1375–1376PubMedCrossRef

31.

Choo HJ, Kim JH, Kwon OB et al (2006) Mitochondria are impaired in the adipocytes of type 2 diabetic mice. Diabetologia 49:784–791PubMedCrossRef

32.

Chance DS, Mcintosh MK (1994) Rates of beta-oxidation of fatty-acids of various chain lengths and degrees of unsaturation in highly purified peroxisomes isolated from rat-liver. Comp Biochem Phys B 109:273–280CrossRef

33.

Shimano H, Matsuzaka T, Yahagi N et al (2007) Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nat Med 13:1193–1202PubMedCrossRef

34.

de Graaf RA, Brown PB, McIntyre S et al (2006) High magnetic field water and metabolite proton T-1 and T-2 relaxation in rat brain in vivo. Magn Reson Med 56:386–394PubMedCrossRef

35.

Delikatny EJ, Chawla S, Leung DJ et al (2011) MR-visible lipids and the tumor microenvironment. NMR Biomed 24:592–611PubMed

36.

Giarola M, Rossi B, Mosconi E et al (2011) Fast and minimally invasive determination of the unsaturation index of white fat depots by micro-raman spectroscopy. Lipids 46:659–667PubMedCrossRef

37.

Machann J, Thamer C, Schnoedt B et al (2006) Hepatic lipid accumulation in healthy subjects: a comparative study using spectral fat-selective MRI and volume-localized H-1-MR spectroscopy. Magn Reson Med 55:913–917PubMedCrossRef

38.

Johnson NA, Walton DW, Sachinwalla T et al (2008) Noninvasive assessment of hepatic lipid composition: advancing understanding and management of fatty liver disorders. Hepatology 47:1513–1523PubMedCrossRef

39.

Yki-Jarvinen H (2005) Fat in the liver and insulin resistance. Ann Med 37:347–356PubMedCrossRef

40.

Li X, Grundy SM, Patel SB (1997) Obesity in db and ob animals leads to impaired hepatic very low density lipoprotein secretion and differential secretion of apolipoprotein B-48 and B-100. J Lipid Res 38:1277–1288PubMed

41.

Dong Z, Dreher W, Leibfritz D et al (2009) Challenges of using MR spectroscopy to detect neural progenitor cells in vivo. Am J Neuroradiol 30:1096–1101PubMedCrossRef

42.

Yahya A, Fallone BG (2010) T(2) determination of the J-coupled methyl protons of lipids: in vivo illustration with tibial bone marrow at 3 T. J Magn Reson Imaging 31:1514–1521PubMedCrossRef

43.

Yahya A, Tessier AG, Fallone BG (2011) Effect of J-coupling on lipid composition determination with localized proton magnetic resonance spectroscopy at 9.4 T. J Magn Reson Imaging 34:1388–1396PubMedCrossRef

44.

Ye Q, Danzer CF, Fuchs A et al (2011) Longitudinal evaluation of intramyocellular lipids (IMCLs) in tibialis anterior muscle of ob/ob and ob/+ control mice using a cryogenic surface coil at 9.4 T. NMR Biomed 24:1295–1301PubMedCrossRef

Title: Hepatic lipid composition differs between ob/ob and ob/+ control mice as determined by using in vivo localized proton magnetic resonance spectroscopy
Authors: Qiong Ye
Carsten Friedrich Danzer
Alexander Fuchs
Christian Wolfrum
Markus Rudin
Publication date: 01-10-2012
Publisher: Springer-Verlag
Published in: Magnetic Resonance Materials in Physics, Biology and Medicine / Issue 5/2012
Print ISSN: 0968-5243
Electronic ISSN: 1352-8661
DOI: https://doi.org/10.1007/s10334-012-0310-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Hepatic lipid composition differs between ob/ob and ob/+ control mice as determined by using in vivo localized proton magnetic resonance spectroscopy

Abstract

Object

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Object

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2012

Detection of ATP by “in line” 31P magnetic resonance spectroscopy during oxygenated hypothermic pulsatile perfusion of pigs’ kidneys

Manganese chloride tetrahydrate (CMC-001) enhanced liver MRI: evaluation of efficacy and safety in healthy volunteers

Absolute quantitation of brain metabolites with respect to heterogeneous tissue compositions in 1H-MR spectroscopic volumes

Correlating brain blood oxygenation level dependent (BOLD) fractal dimension mapping with magnetic resonance spectroscopy (MRS) in Alzheimer’s disease

A multimodal imaging approach to the evaluation of post-traumatic epilepsy

Minimization of spectral pattern changes during HRMAS experiments at 37 degrees celsius by prior focused microwave irradiation