Long-echo time MR spectroscopy for skeletal muscle acetylcarnitine detection

L. Lindeboom, C.I. Nabuurs, J. Hoeks, B. Brouwers, E. Phielix, M.E. Kooi, M.K. Hesselink, J.E. Wildberger, R.D. Stevens, T. Koves, D. M. Muoio, P. Schrauwen, V.B. Schrauwen-Hinderling

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Abstract

Animal models suggest that acetylcarnitine production is essential for maintaining metabolic flexibility and insulin sensitivity. Because methods to detect acetylcarnitine involve biopsy of the tissue of noninvasive alternatives to measure acetylcarnitine concentrations could facilitate our understanding of its physiological relevance in humans. investigated the use of long-echo time (TE) proton magnetic resonance spectroscopy (1H-MRS) to measure skeletal muscle acetylcarnitine on a clinical 3T scanner. We applied long-TE 1H-MRS to measure endurance-trained athletes, lean and obese sedentary subjects, and type diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE 1H-MRS protocol was implemented for successful of skeletal muscle acetylcarnitine in these individuals. There were differences in insulin sensitivity, as measured by hyperinsulinemic- clamp, and skeletal muscle mitochondrial function, as measured by (31P-MRS), across groups. Insulin sensitivity and mitochondrial function highest in trained athletes and lowest in T2DM patients. Skeletal muscle acetylcarnitine concentration showed a reciprocal distribution, with acetylcarnitine concentration correlating with mean insulin sensitivity group. These results demonstrate that measuring acetylcarnitine with 1H-MRS is feasible on clinical MR scanners and support the T2DM patients are characterized by a decreased formation of possibly underlying decreased insulin sensitivity.
Original languageEnglish
Pages (from-to)4915-4925
Number of pages11
JournalJournal of Clinical Investigation
Volume124
Issue number11
DOIs
Publication statusPublished - Nov 2014

Keywords

  • INSULIN-RESISTANCE
  • LIPID-CONTENT
  • MALONYL-COA
  • 3 T
  • CARNITINE
  • EXERCISE
  • METABOLISM
  • QUANTIFICATION
  • PERFORMANCE
  • OXIDATION

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