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Intramyocellular Lipids (intramyocellular + lipid)
Selected AbstractsStandardized protocol for a depletion of intramyocellular lipids (IMCL)NMR IN BIOMEDICINE, Issue 5 2010Michael Ith Abstract Intramyocellular lipids (IMCL) are flexible fuel stores that are depleted by physical exercise and replenished by fat intake. IMCL or their degradation products are thought to interfere with insulin signaling thereby contributing to insulin resistance. From a practical point of view it is desirable to deplete IMCL prior to replenishing them. So far, it is not clear for how long and at which intensity subjects have to exercise in order to deplete IMCL. We therefore aimed at developing a standardized exercise protocol that is applicable to subjects over a broad range of exercise capacity and insulin sensitivity and allows measuring reliably reduced IMCL levels. Twelve male subjects, including four diabetes type 2 patients, with wide ranges of exercise capacity (VO2peak per total body weight 27.9,55.8,ml*kg,1*min,1), insulin sensitivity (glucose infusion rate per lean body mass 4.7,15.3,mg*min,1*kg,1), and BMI (21.7,31.5,kg*m,2), respectively, were enrolled. Using 1H magnetic resonance spectroscopy (1H-MRS), IMCL was measured in m.tibialis anterior and m.vastus intermedius before and during a depletion protocol of a week, consisting of a moderate additional physical activity (1,h daily at 60% VO2peak) and modest low-fat (10,15%) diet. Absolute IMCL-levels were significantly reduced in both muscles during the first 3 days and stayed constant for the next 3 days of an identical diet/exercise-scheme. These reduced IMCL levels were independent of insulin sensitivity, yet a tendency to lower depleted IMCL levels has been observed in subjects with higher VO2peak. The proposed protocol is feasible in subjects with large differences in exercise capacity, insulin sensitivity, and BMI, leading to reduced IMCL levels that neither depend on the exact duration of the depletion protocol nor on insulin sensitivity. This allows for a standardized preparation of IMCL levels either for correlation with other physiological parameters or for replenishment studies. Copyright © 2010 John Wiley & Sons, Ltd. [source] Effects of cevoglitazar, a dual PPAR,/, agonist, on ectopic fat deposition in fatty Zucker ratsDIABETES OBESITY & METABOLISM, Issue 6 2009D. Laurent Aim:, By acting as both insulin sensitizers and lipid-lowering agents, dual-acting peroxisome proliferator-activated receptors ,/, (PPAR,/,) agonists may be used to improve glucose tolerance in type 2 diabetic patients without inducing adiposity and body weight gain. Here, in an animal model of obesity and insulin resistance, the metabolic response to cevoglitazar, a dual PPAR,/,, was characterized using a combination of in vivo and ex vivo magnetic resonance methodologies and compared to treatment effects of fenofibrate, a PPAR, agonist, and pioglitazone, a PPAR, agonist. Methods:, Four groups of fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii) pioglitazone 30 mg/kg; and (iv) cevoglitazar 5 mg/kg were investigated before and after treatment. Animals were fed a fat-enriched (54% kcal fat) diet for 6 weeks, 2 weeks high of fat,exposure alone followed by a 4-week dosing period. Results and conclusions:, Cevoglitazar was as effective as pioglitazone at improving glucose tolerance. However, unlike pioglitazone, both fenofibrate and cevoglitazar reduced BW gain and adiposity, independent of food intake. All three treatment regimens normalized intramyocellular lipids. Metabolic profiling showed that in the muscle cevoglitazar improves the lipid profile via both PPAR,- and PPAR,-mediated mechanisms. Pioglitazone reduced hepatic lipid accumulation, while cevoglitazar and fenofibrate reduced hepatic lipid concentration below baseline levels (p < 0.05). Metabolic profiling showed that in the liver, cevoglitazar functions largely through PPAR, agonism resulting in increased ,-oxidation. Cevoglitazar only induced small changes to the lipid composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced changes similar to those observed with fenofibrate suggesting export of fatty acids from this depot. [source] Inductively coupled helmholtz coil on a dedicated imaging platform for the in vivo1H-MRS measurement of intramyocellular lipids in the hind leg of ratsMAGNETIC RESONANCE IN MEDICINE, Issue 4 2009Michael Neumaier PhD Abstract Skeletal muscle triglycerides are markers for insulin resistance in type 2 diabetes. Recently, MR spectroscopy was adapted for in vivo measurement of triglycerides in animal models and for the characterization of new therapeutic approaches. Because of small MR spectroscopy voxel sizes used in skeletal muscles, surface coils are used for signal reception. Furthermore, to obtain well-resolved and undistorted lipid spectra, muscle fibers must be aligned parallel to the magnetic field. Consequently, to achieve a high signal-to-noise ratio and spectral quality, a coil setup must combine high sensitivity with a reliable and reproducible positioning of muscle and voxel. These demands are difficult to match using surface coils. Here, a coil platform is described, which uses inductively coupled Helmholtz coil setup combined with a leg retainer system for rats. The new system allows for measurement of intramyocellular lipids with high signal-to-noise ratio and for significantly improved animal handling, positioning, and throughput. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source] Standardized protocol for a depletion of intramyocellular lipids (IMCL)NMR IN BIOMEDICINE, Issue 5 2010Michael Ith Abstract Intramyocellular lipids (IMCL) are flexible fuel stores that are depleted by physical exercise and replenished by fat intake. IMCL or their degradation products are thought to interfere with insulin signaling thereby contributing to insulin resistance. From a practical point of view it is desirable to deplete IMCL prior to replenishing them. So far, it is not clear for how long and at which intensity subjects have to exercise in order to deplete IMCL. We therefore aimed at developing a standardized exercise protocol that is applicable to subjects over a broad range of exercise capacity and insulin sensitivity and allows measuring reliably reduced IMCL levels. Twelve male subjects, including four diabetes type 2 patients, with wide ranges of exercise capacity (VO2peak per total body weight 27.9,55.8,ml*kg,1*min,1), insulin sensitivity (glucose infusion rate per lean body mass 4.7,15.3,mg*min,1*kg,1), and BMI (21.7,31.5,kg*m,2), respectively, were enrolled. Using 1H magnetic resonance spectroscopy (1H-MRS), IMCL was measured in m.tibialis anterior and m.vastus intermedius before and during a depletion protocol of a week, consisting of a moderate additional physical activity (1,h daily at 60% VO2peak) and modest low-fat (10,15%) diet. Absolute IMCL-levels were significantly reduced in both muscles during the first 3 days and stayed constant for the next 3 days of an identical diet/exercise-scheme. These reduced IMCL levels were independent of insulin sensitivity, yet a tendency to lower depleted IMCL levels has been observed in subjects with higher VO2peak. The proposed protocol is feasible in subjects with large differences in exercise capacity, insulin sensitivity, and BMI, leading to reduced IMCL levels that neither depend on the exact duration of the depletion protocol nor on insulin sensitivity. This allows for a standardized preparation of IMCL levels either for correlation with other physiological parameters or for replenishment studies. Copyright © 2010 John Wiley & Sons, Ltd. [source] Role of proton MR for the study of muscle lipid metabolism,NMR IN BIOMEDICINE, Issue 7 2006Chris Boesch Abstract 1H-MR spectroscopy (MRS) of intramyocellular lipids (IMCL) became particularly important when it was recognized that IMCL levels are related to insulin sensitivity. While this relation is rather complex and depends on the training status of the subjects, various other influences such as exercise and diet also influence IMCL concentrations. This may open insight into many metabolic interactions; however, it also requires careful planning of studies in order to control all these confounding influences. This review summarizes various historical, methodological, and practical aspects of 1H-MR spectroscopy (MRS) of muscular lipids. That includes a differentiation of bulk magnetic susceptibility effects and residual dipolar coupling that can both be observed in MRS of skeletal muscle, yet affecting different metabolites in a specific way. Fitting of the intra- (IMCL) and extramyocellular (EMCL) signals with complex line shapes and the transformation into absolute concentrations is discussed. Since the determination of IMCL in muscle groups with oblique fiber orientation or in obese subjects is still difficult, potential improvement with high-resolution spectroscopic imaging or at higher field strength is considered. Fat selective imaging is presented as a possible alternative to MRS and the potential of multinuclear MRS is discussed. 1H-MRS of muscle lipids allows non-invasive and repeated studies of muscle metabolism that lead to highly relevant findings in clinics and patho-physiology. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||