Correlation between insulin resistance and intramyocellular lipid levels in rats

Kuhlmann, Johanna; Neumann-Haefelin, Claudia; Belz, Ulrich; Kramer, Werner; Juretschke, Hans-Paul; Herling, Andreas W.

doi:10.1002/mrm.20501

Cited by 32 publications

(32 citation statements)

References 44 publications

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“…Accordingly, exercise training during the final 4 weeks of the 12-week dietary intervention increased the insulin sensitivity index proportionally to the decrease in IMCL. Therefore, our current findings corroborate earlier findings in both rodents (51) and humans (7) showing close associations between IMCL accumulation, due to an increased fat supply to muscles, and insulin sensitivity. A recent study by Holloway and co-workers have also demonstrated that as FFA transport in muscles from obese rats is increased by virtue of elevated circulating FFA concentration in conjunction with increased capacity for membrane FFA transport, the rate of intramyocellular triacylglycerol accumulation occurs at a much greater rate than the compensatory increase in the rate of mitochondrial fat oxidation (8).…”

Section: Discussionsupporting

confidence: 93%

Hyperglycemic diet and training alter insulin sensitivity, intramyocellular lipid content but not UCP3 protein expression in rat skeletal muscles

Vaisy

Szlufcik²,

Maris³

et al. 2010

Int J Mol Med

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Abstract. Intramyocellular lipids (IMCL) and mitochondrial uncoupling protein-3 (UCP3) have been implicated in the development of muscular insulin resistance. This study aimed to investigate the role of IMCL and UCP3 in the development of glucose intolerance and muscular insulin resistance during 12 weeks of an obesity-inducing 'cafeteria-style' diet alone (CAF), or in conjunction with exercise training from weeks 8-12 (CAF TR ), in rats. At the end of the intervention period, gain in body weight was 20% higher in CAF (305±10 g) than controls (CON) (255±14 g; p<0.001) and CAF TR (253±7 g; p<0.001). Furthermore, compared with CON, the Matsuda insulin sensitivity index (ISI), assessed during a 2-h intravenous glucose tolerance test, was markedly lower in CAF (6.7±0.4) than in either CON (15.6±1.4; p<0.001) or CAF TR (11.2±1.1; p<0.001). Moreover, in CAF glucose transport at a submaximal insulin concentration (200 μU/ml) was reduced by ~60% (p<0.05) in both red and white gastrocnemius muscles, but not in m. soleus. However, glucose transport in CAF TR was similar to CON in red gastrocnemius. In CAF fiber-specific IMCL content determined in m. soleus and extensor digitorum longus (EDL), was higher than in CON (p<0.01) and CAF TR (p<0.001). Muscle UCP3 protein content was not changed by any of the interventions. Interestingly, within CAF and CAF TR , ISI closely negatively correlated with IMCL content in both type I (soleus, r=-0.93; EDL, r=-0.90; p<0.05) and IIa (EDL, r=-0.52, p<0.05) muscle fibers. These findings indicate that changes in IMCL content but not UCP3 content are implicated in short-term effects of cafeteria-style diet and exercise training on muscular insulin sensitivity in rats.

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Section: Discussionsupporting

confidence: 93%

Hyperglycemic diet and training alter insulin sensitivity, intramyocellular lipid content but not UCP3 protein expression in rat skeletal muscles

Vaisy

Szlufcik²,

Maris³

et al. 2010

Int J Mol Med

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“…When fat storage in rat skeletal muscle is studied, the IMCL is usually normalized to the tCr signal (3,6,7,16,17). In human studies, however, the IMCL is often expressed as a percentage of the water signal originating from the same voxel, since the tCr signal is small compared to the IMCL signal and is not easy to quantify at commonly used clinical field strengths (18).…”

Section: Discussionmentioning

confidence: 99%

“…IMCL itself probably does not interfere with the insulin signaling pathway directly; rather, it is considered a surrogate marker of lipid metabolites, such as long chain acyl-CoA, diacylglycerol, and ceramides, that are likely to induce defects in the insulin signaling cascade (2). The good correlation of IMCL with insulin sensitivity led to the suggestion that IMCL could be used as a biomarker for insulin resistance in rat models (3).…”

mentioning

confidence: 99%

Regional variations in intramyocellular lipid concentration correlate with muscle fiber type distribution in rat tibialis anterior muscle

Feyter

Schaart

Hesselink

et al. 2006

Magnetic Resonance in Med

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1 1 H MR spectroscopy (MRS) has proved to be a valuable noninvasive tool to measure intramyocellular lipids (IMCL) in research focused on insulin resistance and type II diabetes in both humans and rodents. An important determinant of IMCL is the muscle fiber type, since oxidative type I fibers can contain up to three times more IMCL than glycolytic type II muscle fibers. Because these different muscle fiber types are inhomogeneously distributed in rodent muscle, in the present study we investigated the distribution of IMCL within the rat tibialis anterior muscle (TA) in vivo using single-voxel 1 H MRS along with the muscle fiber distribution in the TA ex vivo determined from immunohistological assays. IMCL levels in the TA differed by up to a factor of 3 depending on the position of the voxel. Skeletal muscle insulin resistance is one of the earliest detectable aberrations in and a predisposing factor for the development of type II diabetes. Increased content of intramyocellular lipids (IMCL) has been closely associated with decreased whole-body and skeletal muscle insulin sensitivity in both healthy and diabetic humans, as well as in animals (reviewed in Ref. 1). IMCL itself probably does not interfere with the insulin signaling pathway directly; rather, it is considered a surrogate marker of lipid metabolites, such as long chain acyl-CoA, diacylglycerol, and ceramides, that are likely to induce defects in the insulin signaling cascade (2). The good correlation of IMCL with insulin sensitivity led to the suggestion that IMCL could be used as a biomarker for insulin resistance in rat models (3).Skeletal muscle stores lipids not only intracellularly, but also extracellularly within interstitial adipocytes. Lipid extraction analysis of muscle biopsy samples therefore cannot differentiate between IMCL and extramyocellular lipids (EMCL) and hence may overestimate the actual IMCL content (1). The discovery that IMCL and EMCL resonate at different frequencies in the 1 H MR spectrum of human skeletal muscle was an important methodological advance in the study of skeletal muscle lipid metabolism (4). The resonance at 1.28 ppm is independent of the angle between the muscle fibers and the static magnetic field, and therefore is attributed to the CH 2 groups of IMCL because IMCL is dispersed as spherical droplets within the muscle cells. The other lipid CH 2 peak shifts with the angle between the muscle fibers and the field, and is therefore attributed to EMCL, which supposedly is arranged in a sheet-like manner along the muscle fibers. The largest chemical shift difference between the two peaks is 0.2 ppm, which is obtained when the muscle fibers are aligned parallel with the magnetic field (5). Since 1 H MRS is a noninvasive method, it allows repetitive analysis of IMCL in the same area. Thus, 1 H MRS-based IMCL measures are especially useful for determining IMCL levels in human studies, as well as for animal intervention and longitudinal studies.Using 1 H MRS, Neumann-Haefelin et al. (6) showed that the IMCL content in ...

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“…In trained athletes this relationship was reversed and high IMCL predicted high insulin sensitivity. In recent years, 1 H-MRS of IMCL has been increasingly used in animals, in particular to study pharmacological interventions and at higher magnetic field strength (23)(24)(25)(26)(27)(28). It would go beyond the target of this review to go into methodological details of these studies since MR examinations in small animals with voxels of a few microliters pose different methodological challenges than MRS in humans.…”

Section: Relation Between Imcl Content and Insulin Sensitivitymentioning

confidence: 99%

Role of proton MR for the study of muscle lipid metabolism

et al. 2006

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1 H-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 1 H-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. 1 H-MRS of muscle lipids allows non-invasive and repeated studies of muscle metabolism that lead to highly relevant findings in clinics and patho-physiology.

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Correlation between insulin resistance and intramyocellular lipid levels in rats

Cited by 32 publications

References 44 publications

Hyperglycemic diet and training alter insulin sensitivity, intramyocellular lipid content but not UCP3 protein expression in rat skeletal muscles

Hyperglycemic diet and training alter insulin sensitivity, intramyocellular lipid content but not UCP3 protein expression in rat skeletal muscles

Regional variations in intramyocellular lipid concentration correlate with muscle fiber type distribution in rat tibialis anterior muscle

Role of proton MR for the study of muscle lipid metabolism

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