Reduction of intramyocellular lipid following short-term rosiglitazone treatment in Zucker fatty rats: An in vivo nuclear magnetic resonance study

Jucker, Beat M.; Schaeffer, Thomas; Haimbach, Robin E.; M, Mayer; Ohlstein, Derek H.; Smith, Stephen A.; Cobitz, Alexander R.; Sarkar, Susanta K.

doi:10.1053/meta.2003.50040

Cited by 25 publications

(24 citation statements)

References 41 publications

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“…However, there is mounting evidence that rosiglitazone acts to improve insulin sensitivity in the absence of decreased muscle lipid storage in humans (9,27) and animal models of insulin resistance (7,10,12,28), suggesting that lipid steal from muscle may not be necessary for rosiglitazone-induced insulin sensitization. Although some investigations have demonstrated that lipid storage is decreased in muscle after rosiglitazone treatment (3,4,24), rosiglitazone-induced reductions of liver lipid accumulation have been more consistently observed (5,7,9,29). In the present study, 4-week rosiglitazone treatment resulted in a 20% increase in muscle TAG content (Fig.…”

Section: Fig 3 Skeletal Muscle Ampk Activity and Protein Expressionsupporting

confidence: 37%

“…It has been suggested that peroxisome proliferator-activated receptor (PPAR) agonists, such as rosiglitazone, improve skeletal muscle insulin sensitivity by preventing the toxic accumulation of lipids in this tissue (3,4). However, the sequestration of lipids from skeletal muscle after chronic rosiglitazone treatment has not been consistently observed (3)(4)(5)(6)(7)(8)(9)(10)(11). There is also evidence that mechanism(s) independent of changes in lipid status (i.e., skeletal muscle AMP-activated protein kinase [AMPK] activation) may be involved in the insulinsensitizing actions of rosiglitazone (12,13).…”

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confidence: 99%

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Tissue-Specific Effects of Rosiglitazone and Exercise in the Treatment of Lipid-Induced Insulin Resistance

et al. 2007

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Both pharmacological intervention (i.e., thiazolidinediones [TZDs]) and lifestyle modification (i.e., exercise training) are clinically effective treatments for improving whole-body insulin sensitivity. However, the mechanism(s) by which these therapies reverse lipid-induced insulin resistance in skeletal muscle is unclear. We determined the effects of 4 weeks of rosiglitazone treatment and exercise training and their combined actions (rosiglitazone treatment and exercise training) on lipid and glucose metabolism in high-fat-fed rats. High-fat feeding resulted in decreased muscle insulin sensitivity, which was associated with increased rates of palmitate uptake and the accumulation of the fatty acid metabolites ceramide and diacylglycerol. Impairments in lipid metabolism were accompanied by defects in the Akt/AS160 signaling pathway. Exercise training, but not rosiglitazone treatment, reversed these impairments, resulting in improved insulinstimulated glucose transport and increased rates of fatty acid oxidation in skeletal muscle. The improvements to glucose and lipid metabolism observed with exercise training were associated with increased AMP-activated protein kinase ␣1 activity; increased expression of Akt1, peroxisome proliferator-activated receptor ␥ coactivator 1, and GLUT4; and a decrease in AS160 expression. In contrast, rosiglitazone treatment exacerbated lipid accumulation and decreased insulin-stimulated glucose transport in skeletal muscle. However, rosiglitazone, but not exercise training, increased adipose tissue GLUT4 and acetyl CoA carboxylase expression. Both exercise training and rosiglitazone decreased liver triacylglycerol content. Although both interventions can improve whole-body insulin sensitivity, our results show that they produce divergent effects on protein expression and triglyceride storage in different tissues. Accordingly, exercise training and rosiglitazone may act as complementary therapies for the treatment of insulin resistance.

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Section: Fig 3 Skeletal Muscle Ampk Activity and Protein Expressionsupporting

confidence: 37%

mentioning

confidence: 99%

Tissue-Specific Effects of Rosiglitazone and Exercise in the Treatment of Lipid-Induced Insulin Resistance

et al. 2007

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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%

“…In recent years, 1 H-MR spectra of IMCL have been acquired at field strengths above 3 T, either in humans (52,98,115) or particularly in small animals (23,25,27,28). These studies show the potential of higher field strengths for a separation of IMCL and EMCL, and particularly the reduction of contamination by EMCL that can be achieved by a smaller voxel size.…”

Section: Influence Of Magnetic Field Strength On 1 H-mr Spectra Of Skmentioning

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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“…6,20,24 Lost muscle strength is associated with the accumulation of EMCLs, which can interfere with sufficient muscle nutrition. 6,24,25 We previously reported that IMCLs using MRS analysis in the Mm of patients with CLBP were significantly higher than in asymptomatic volunteers. 26 Some reports have described the associations of spinopelvic alignment with LBP [27][28][29] and fatty atrophy of Mm; 7,30 however, the association of IMCLs and EMCLs with spinopelvic alignment in patients with CLBP remains unclear.…”

Section: Introductionmentioning

confidence: 97%

Magnetic resonance spectroscopic analysis of multifidus muscles lipid content and association with spinopelvic malalignment in chronic low back pain

Ogon

Takebayashi

Takashima

et al. 2017

BJR

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Objective: To analyze intramyocellular lipids (IMCLs) and extramyocellular lipids (EMCLs) of the multifidus muscle (Mm) using MR spectroscopy in chronic low back pain (CLBP) and control groups and to identify correlations with spinopelvic alignment. Methods: 40 patients (16 males, 24 females; mean age, 62.9 6 1.9 years) whose visual analogue scale scores were .30 mm for CLBP were included. Furthermore, 40 control participants matched with the CLBP group subjects by sample size, gender and age (17 males, 23 females; mean age, 65.0 6 1.2 years) were included. We compared the body mass index, physical workload, leisure time physical activity level, spinopelvic parameters, and IMCLs and EMCLs of the Mm between the groups. We also evaluated possible correlations of spinopelvic parameters with IMCLs and EMCLs of the Mm in the groups.

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Reduction of intramyocellular lipid following short-term rosiglitazone treatment in Zucker fatty rats: An in vivo nuclear magnetic resonance study

Cited by 25 publications

References 41 publications

Tissue-Specific Effects of Rosiglitazone and Exercise in the Treatment of Lipid-Induced Insulin Resistance

Tissue-Specific Effects of Rosiglitazone and Exercise in the Treatment of Lipid-Induced Insulin Resistance

Role of proton MR for the study of muscle lipid metabolism

Magnetic resonance spectroscopic analysis of multifidus muscles lipid content and association with spinopelvic malalignment in chronic low back pain

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