The reason for the 3-to 4-h delay between a rise in plasma free fatty acid (FFA) levels and the development of insulin resistance remains unknown. In the current study, we have tested the hypothesis that the delay may be caused by the need for plasma FFAs to first enter muscle cells and to be re-esterified there before causing insulin resistance. To this end, we have determined intramyocellular triglyceride (IMCL-TG) content with proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy in healthy volunteers before and 4 h after lowering of plasma FFAs (with euglycemic-hyperinsulinemic clamping) or after increasing plasma FFAs (with lipid plus heparin infusions). Increasing plasma FFAs (from 516 to 1,207 mol/l or from 464 to 1,857 mol/l, respectively) was associated with acute increases in IMCL-TG from 100 to 109 ؎ 5% (P < 0.05) or to 133 ؎ 11% (P < 0.01), respectively, and with a significant increase in insulin resistance (P < 0.05 after 3.5 h). Lowering of plasma FFAs from 560 to 41 mol/l was associated with a tendency for IMCL-TG to decrease (from 100 to 95 ؎ 3%). Changes in plasma FFAs correlated linearly with IMCL-TG (r ؍ 0.74, P < 0.003). The demonstration that acute changes in plasma FFAs were accompanied by corresponding changes in IMCL-TG and with the development of insulin resistance, taken together with previous reports of a close correlation between IMCL-TG and insulin resistance, supported the notion that accumulation of IMCL-TG is a step in the development of FFA-induced insulin resistance.
Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.
Purpose:To demonstrate the feasibility of estimating the relative intra-and extramyocellular lipid (IMCL and EMCL) pool magnitudes and calculating the degree of lipid unsaturation within soleus muscle using single-voxel localized oneand two-dimensional (1D and 2D) MR spectroscopy (MRS).
Materials and Methods:Localized 1D point resolved spectroscopy (PRESS) and 2D correlation spectroscopy (L-COSY) were performed in identical locations in the soleus muscle of 10 healthy subjects. A GE 3-T MRI/MRS scanner and a quadrature extremity transmit/receive coil was used.
Results:The 1D and 2D MR spectra were used to compute IMCL/creatine (Cr) and EMCL/Cr ratios. In addition to cross peaks between the methyl and methylene protons in the high-field region, the 2D spectra showed cross peaks due to J-coupling between allylic, diallylic methylene protons, and olefinic protons. The cross-peak volume ratios also provided a measure of double bonds, suggesting that this ratio can be used to assess unsaturation within IMCL and EMCL lipid pools.
Conclusion:We have demonstrated the feasibility of detecting 2D cross peaks between different groups of IMCL and EMCL, including the unsaturated protons within these two lipids pools. This protocol may be easily extended to study the lipids present in other tissues.
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