31P-Magnetization Transfer Magnetic Resonance Spectroscopy Measurements of In Vivo Metabolism

被引:48
作者
Befroy, Douglas E. [1 ,2 ]
Rothman, Douglas L. [1 ,3 ]
Petersen, Kitt Falk [2 ]
Shulman, Gerald I. [2 ,4 ,5 ]
机构
[1] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA
[2] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA
[3] Yale Univ, Sch Med, Dept Biomed Engn, New Haven, CT USA
[4] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA
[5] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA
关键词
PHOSPHOCREATINE RECOVERY KINETICS; NMR SATURATION-TRANSFER; HUMAN SKELETAL-MUSCLE; INTRAMYOCELLULAR LIPID-CONTENT; STIMULATED ATP SYNTHESIS; HIGH-FAT-DIET; ENERGY-METABOLISM; MITOCHONDRIAL-FUNCTION; UNCOUPLING PROTEIN-3; OXIDATIVE CAPACITY;
D O I
10.2337/db12-0558
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Magnetic resonance spectroscopy offers a broad range of noninvasive analytical methods for investigating metabolism in vivo. Of these, the magnetization-transfer (MT) techniques permit the estimation of the unidirectional fluxes associated with metabolic exchange reactions. Phosphorus (P-31) MT measurements can be used to examine the bioenergetic reactions of the creatine-kinase system and the ATP synthesis/hydrolysis cycle. Observations from our group and others suggest that the inorganic phosphate (P-i) -> ATP flux in skeletal muscle may be modulated by certain conditions, including aging, insulin resistance, and diabetes, and may reflect inherent alterations in mitochondrial metabolism. However, such effects on the P-i -> ATP flux are not universally observed under conditions in which mitochondrial function, assessed by other techniques, is impaired, and recent articles have raised concerns about the absolute magnitude of the measured reaction rates. As the application of P-31-MT techniques becomes more widespread, this article reviews the methodology and outlines our experience with its implementation in a variety of models in vivo. Also discussed are potential limitations of the technique, complementary methods for assessing oxidative metabolism, and whether the P-i -> ATP flux is a viable biomarker of metabolic function in vivo. Diabetes 61:2669-2678, 2012
引用
收藏
页码:2669 / 2678
页数:10
相关论文
共 104 条
[41]   OXYGEN COST OF TWITCH AND TETANIC ISOMETRIC CONTRACTIONS OF RAT SKELETAL-MUSCLE [J].
HOOD, DA ;
GORSKI, J ;
TERJUNG, RL .
AMERICAN JOURNAL OF PHYSIOLOGY, 1986, 250 (04) :E449-E456
[42]   RELATIONSHIP BETWEEN MITOCHONDRIA AND OXYGEN-CONSUMPTION IN ISOLATED CAT MUSCLES [J].
HOPPELER, H ;
HUDLICKA, O ;
UHLMANN, E .
JOURNAL OF PHYSIOLOGY-LONDON, 1987, 385 :661-675
[43]   Quantitative mathematical expressions for accurate in vivo assessment of cytosolic [ADP] and ΔG of ATP hydrolysis in the human brain and skeletal muscle [J].
Iotti, S ;
Frassineti, C ;
Sabatini, A ;
Vacca, A ;
Barbiroli, B .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2005, 1708 (02) :164-177
[44]   Assessment of mitochondrial energy coupling in vivo by 13C/31P NMR [J].
Jucker, BM ;
Dufour, S ;
Ren, JM ;
Cao, XY ;
Previs, SF ;
Underhill, B ;
Cadman, KS ;
Shulman, GI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) :6880-6884
[45]   13C/31P NMR assessment of mitochondrial energy coupling in skeletal muscle of awake fed and fasted rats -: Relationship with uncoupling protein 3 expression [J].
Jucker, BM ;
Ren, JM ;
Dufour, S ;
Cao, XY ;
Previs, SF ;
Cadman, KS ;
Shulman, GI .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (50) :39279-39286
[46]  
Kemp GJ, 2008, AM J PHYSIOL-ENDOC M, V294, P643
[47]   Correcting for incomplete saturation and off-resonance effects in multiple-site saturation-transfer kinetic measurements [J].
Kingsley, PB ;
Monahan, WG .
JOURNAL OF MAGNETIC RESONANCE, 2000, 146 (01) :100-109
[48]   Effects of off-resonance irradiation, cross-relaxation, and chemical exchange on steady-state magnetization and effective spin-lattice relaxation times [J].
Kingsley, PB ;
Monahan, WG .
JOURNAL OF MAGNETIC RESONANCE, 2000, 143 (02) :360-375
[49]   P-31 NMR-STUDIES OF ATP SYNTHESIS AND HYDROLYSIS KINETICS IN THE INTACT MYOCARDIUM [J].
KINGSLEYHICKMAN, PB ;
SAKO, EY ;
MOHANAKRISHNAN, P ;
ROBITAILLE, PML ;
FROM, AHL ;
FOKER, JE ;
UGURBIL, K .
BIOCHEMISTRY, 1987, 26 (23) :7501-7510
[50]  
LANDIN K, 1991, J HYPERTENS, V9, P65