Muscle-Specific Relation of Acetylcarnitine and Intramyocellular Lipids to Chronic Hyperglycemia: A Pilot 3-T 1H MRS Study

Radka Klepochová, Michael Leutner, Magdalena Bastian, Michael Krebs, Michael Weber, Siegfried Trattnig, Alexandra Kautzky-Willer, Martin Krššák, Radka Klepochová, Michael Leutner, Magdalena Bastian, Michael Krebs, Michael Weber, Siegfried Trattnig, Alexandra Kautzky-Willer, Martin Krššák

Abstract

Objective: Acetylcarnitine plays an important role in fat metabolism and can be detected in proton magnetic resonance spectra in skeletal muscle. An inverse relationship of acetylcarnitine to intramyocellular lipids and metabolic markers of chronic hyperglycemia has been suggested. This study aimed to compare the acetylcarnitine concentrations and intramyocellular lipids measured noninvasively by proton magnetic resonance spectroscopy (1H MRS) in the tibialis anterior and the soleus of three different groups of volunteers with a broad range of glycemic control.

Methods: Acetylcarnitine and intramyocellular lipid concentrations were measured in 35 individuals stratified into three groups according to glucose tolerance and/or manifestation of type 2 diabetes mellitus. All MRS measurements were performed on a 3-T MR system.

Results: The differences in patient phenotype were mirrored by increased intramyocellular lipids in the tibialis anterior and decreased acetylcarnitine concentrations in the soleus muscle of type 2 diabetes patients when compared with normal glucose-tolerant individuals. Results suggest that intramyocellular lipids mirror whole-body glucose tolerance better in the tibialis anterior muscle, whereas acetylcarnitine is a better discriminator in the soleus muscle.

Conclusions: This muscle-specific behavior of metabolites could represent different fiber compositions in the examined muscles and should be considered when planning future metabolic studies.

Trial registration: ClinicalTrials.gov NCT04011228.

Conflict of interest statement

The authors declared no conflict of interest.

© 2020 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).

Figures

Figure 1
Figure 1
Transversal and sagittal slices of T1‐weighted localizer images with representative volume of interest (VOI) positions in the (A,B) soleus and (C,D) tibialis anterior muscle. Green (outer) VOI depicts shimming volume, yellow (middle) VOI reflects acetylcarnitine volume, and red (inner) VOI is for intramyocellular lipids. [Color figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
Representative acetylcarnitine spectrum (red/thick lines) showing final spectral fit (black lines) and residual (blue/bottom lines) from the soleus (left) and the tibialis anterior (right) muscle in (A,B) normal glucose tolerance and (B,D) type 2 diabetes mellitus. In each spectrum, the acetylcarnitine area around 2.14 ppm is enlarged. TMA, trimethyl ammonium. [Color figure can be viewed at wileyonlinelibrary.com]
Figure 3
Figure 3
Boxplots showing concentrations (mean ± SD) of (A) acetylcarnitine and (B) intramyocellular lipids in the soleus and the tibialis anterior muscle in individuals with normal glucose tolerance (NGT), patients with impaired glucose tolerance (IGT), and patients with type 2 diabetes mellitus (T2DM). *Significant difference between the concentrations of acetylcarnitine and intramyocellular lipids within the soleus and the tibialis anterior muscles among groups. Results of acetylcarnitine are given in absolute units as a concentration (mmol/L tissue volume) and intramyocellular lipids as a percentage of water content.
Figure 4
Figure 4
Plots of correlations from all volunteers: (A) acetylcarnitine concentration in the soleus muscle and the tibialis anterior muscle in relation to HbA1C and (B) intramyocellular lipids in the soleus and tibialis anterior muscle in relation to HbA1C. Results of acetylcarnitine are given in absolute units as a concentration (mmol/L tissue volume) and intramyocellular lipids as a percentage of water content.

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