Abstract
Quantifying the amounts and types of lipids present in mixtures is important in fields as diverse as medicine, food science, and biochemistry. Nuclear magnetic resonance (NMR) spectroscopy can quantify the total amounts of saturated and unsaturated fatty acids in mixtures, but identifying the length of saturated fatty acid or the position of unsaturation by NMR is a daunting challenge. We have developed an NMR technique, aliphatic chain length by isotropic mixing, to address this problem. Using a selective total correlation spectroscopy technique to excite and transfer magnetization from a resolved resonance, we demonstrate that the time dependence of this transfer to another resolved site depends linearly on the number of aliphatic carbons separating the two sites. This technique is applied to complex natural mixtures allowing the identification and quantification of the constituent fatty acids. The method has been applied to whole adipocytes demonstrating that it will be of great use in studies of whole tissues.
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References
AOAC (1995) Official methods of analysis of AOAC international. AOAC International, Gaithersburg, MD
AOCS Lipid Library (2014) http://lipidlibrary.aocs.org/
Boslem E, Weir JM, MacIntosh G, Sue N, Cantley J, Meikle PJ, Biden TJ (2013) Alteration of endoplasmic reticulum lipid rafts contributes to lipotoxicity in pancreatic β-cells. J Biol Chem 288:26569–26582
Braunschweiler L, Ernst RR (1983) Coherence transfer by isotropic mixing: application to proton correlation spectroscopy. J Magn Reson 53:521–528
Camont L, Lhomme M, Rached F, Goff WL, Nègre-Salvayre A, Salvayre R, Calzada C, Lagarde M, Chapman MJ, Kontush A (2013) Small, dense high-density lipoprotein-3 particles are enriched in negatively charged phospholipids: relevance to cellular cholesterol efflux, antioxidative, antithrombotic, anti-inflammatory, and antiapoptotic functionalities. Arterioscler Thromb Vasc Biol 33:2715–2723
Casado B, Affolter M, Kussmann M (2009) OMICS-rooted studies of milk proteins, oligosaccharides and lipids. J Proteomics 73:196–208
Didangelos A, Stegemann C, Mayr M (2012) The-omics era: proteomics and lipidomics in vascular research. Atherosclerosis 221:12–17
Ernst RR, Bodenhausen G, Wokaun A (1990) Principles of nuclear magnetic resonance in one and two dimensions. International series of monographs on chemistry. Clarendon Press, Oxford
Fedor D, Kelley DS (2009) Prevention of insulin resistance by n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care 12:138–146
Gelman A, Carlin JB, Stern HS, Rubin DB (2004) Bayesian data analysis, 2nd edn. CRC Press, Boca Raton
Gonzalez-Covarrubias V (2013) Lipidomics in longevity and healthy aging. Biogerontology 14:663–672
Gross RW, Han X (2007) Lipidomics in diabetes and the metabolic syndrome. Methods Enzymol 433:73–90
Guillén MD, Ruiz A (2001) High resolution 1H nuclear magnetic resonance in the study of edible oils and fats. Trends Food Sci Tech 12:328–338
Kamphorst JJ, Cross JR, Fan J, de E Stanchina, Mathew R, White EP, Thompson CB, Rabinowitz JD (2013) Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci USA 110:8882–8887
Kessler H, Oschkinat H, Griesinger C, Bermel W (1986) Transformation of homonuclear two-dimensional NMR techniques into one-dimensional techniques using Gaussian pulses. J Magn Reson 70:106–133
Kien CL, Bunn JY, Poynter ME, Stevens R, Bain J, Ikayeva O, Fukagawa NK, Champagne CM, Crain KI, Koves TR, Muoio DM (2013) A lipidomics analysis of the relationship between dietary fatty acid composition and insulin sensitivity in young adults. Diabetes 62:1054–1063
Kontush A, Chapman MJ (2010) Lipidomics as a tool for the study of lipoprotein metabolism. Curr Atheroscler Rep 12:194–201
Kwan HY, Hu YM, Chan CL, Cao HH, Cheng CY, Pan SY, Tse KW, Wu YC, Yu ZL, Fong WF (2013) Lipidomics identification of metabolic biomarkers in chemically induced hypertriglyceridemic mice. J Proteome Res 12:1387–1398
Li M, Fu W, Li X-A (2010) Differential fatty acid profile in adipose and non-adipose tissues in obese mice. Int J Clin Exp Med 3(4):303–307
Longobardi F, Sacco D, Casiello G, Ventrella A, Contessa A, Sacco A (2012) Garganica kid goat meat: physico-chemical characterization and nutritional impacts. J Food Compost Anal 28(2):107–113
Meikle PJ, Christopher MJ (2011) Lipidomics is providing new insight into the metabolic syndrome and its sequelae. Curr Opin Lipidol 22:210–215
Merched AJ, Chan L (2013) Nutrigenetics and nutrigenomics of atherosclerosis. Curr Atheroscler Rep 15. doi:10.1007/s11883-013-0328-6
O’Donnell VB, Maskrey B, Taylor GW (2009) Eicosanoids: generation and detection in mammalian cells. In: Larijani B et al. (eds) Lipid signaling protocols. Humana Press, Totowa, N.J., pp 5–23. doi:10.1007/978-1-60327-115-8_1
Rasmiena AA, Ng TW, Meikle PJ (2013) Metabolomics and ischaemic heart disease. Clin Sci 124:289–306
Riccardi G, Giacco R, Rivellese AA (2004) Dietary fat, insulin sensitivity and the metabolic syndrome. Clin Nutr 23:447–456
Rule GS, Hitchens TK (2006) Fundamentals of protein NMR spectroscopy. Focus on structural biology. Springer, Dordrecht
Sachleben JR (2006) Bayesian and information theory analysis of MAS sideband patterns in spin 1/2 systems. J Magn Reson 183:123–133
Sbihi HM, Nehdi IA, Al-Resayes SI (2013) Characterization of Hachi (Camelus dromedarius) fat extracted from the hump. Food Chem 139(1–4):649–654
Simonsen N, Pvt Veer, Strain JJ, Martin-Moreno JM, Huttunen JK, Navajas JFC, Martin BC, Thamm M, Kardinaal AFM, Kok FJ, Kohlmeier L (1998) Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. Am J Epidemiol 147:342–352
Sivia DS (1996) Data analysis: a bayesian tutorial. Clarendon Press, Oxford
Ståhlman M, Pham HT, Adiels M, Mitchell TW, Blanksby SJ, Fagerberg B, Ekroos K, Borén J (2012) Clinical dyslipidaemia is associated with changes in the lipid composition and inflammatory properties of apolipoprotein-B-containing lipoproteins from women with type 2 diabetes. Diabetologia 55:1156–1166
Stonehouse J, Adell P, Keeler J, Shaka AJ (1994) Ultrahigh-quality NOE spectra. J Am Chem Soc 116:6037–6038
Stott K, Stonehouse J, Keeler J, Hwang TL, Shaka AJ (1995) Excitation sculpting in high-resolution nuclear magnetic resonance spectroscopy: application to selective NOE experiments. J Am Chem Soc 117:4199–4200
Tallman DL, Taylor CG (2003) Effects of dietary fat and zinc on adiposity, serum leptin, and adipose fatty acid composition in C57BL/6 J mice. J Nutr Biochem 14:17–23
Thiebaut ACM, Chajes V, Gerber M, Boutron-Rualt MC, Joulin V, Lenoir G, Berrino F, Riboli E, Benichou J, Clavel-Chapelon F (2009) Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer 124:924–931
Thrippleton MJ, Keeler J (2003) Elimination of zero-quantum interference in two-dimensional NMR spectra. Angew Chem Int Ed 42:3938–3941
Van QN, Shaka AJ (1998) Improved cross peak detection in two-dimensional proton NMR spectra using excitation sculpting. J Magn Reson 132:154–158
Watson AD (2006) Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. J Lipid Res 47:2101–2111
Acknowledgments
We would like to thank Stephen Meredith and Shohei Koide for useful discussion and comments. This work was supported by NIH R01-CA148814 (S.D. Conzen), DOD predoctoral fellowship W81XWH-11-1-014901 (P.A. Volden) and by the Biological Sciences Division, the Office of Shared Research Facilities, and the Department of Biochemistry and Molecular Biology (J.R. Sachleben) at the University of Chicago.
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Sachleben, J.R., Yi, R., Volden, P.A. et al. Aliphatic chain length by isotropic mixing (ALCHIM): determining composition of complex lipid samples by 1H NMR spectroscopy. J Biomol NMR 59, 161–173 (2014). https://doi.org/10.1007/s10858-014-9836-0
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DOI: https://doi.org/10.1007/s10858-014-9836-0