Muscle-Type Specific Intramyocellular and Hepatic Lipid Metabolism During Starvation in Wistar Rats

Neumann-Haefelin, Claudia; Beha, Anja; Kuhlmann, Johanna; Belz, Ulrich; Gerl, Martin; Quint, M.; Biemer‐Daub, Gabriele; Bröenstrup, Mark; Stein, Marion; Kleinschmidt, Elke; Schaefer, Hans-Ludwig; Schmoll, Dieter; Kramer, Werner; Juretschke, Hans-Paul; Herling, Andreas W.

doi:10.2337/diabetes.53.3.528

Cited by 28 publications

(28 citation statements)

References 53 publications

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“…It can be speculated that after 6 weeks of treatment, steady state reduction of visceral fat was not completely achieved and therefore increased lipolysis from visceral fat drained to the liver was still responsible for increased HepCL, and that a prolongation of the rimonabant treatment would finally result in a decrease of HepCL, too, similar to the decreased IMCL levels, which demonstrated much faster dynamics. 30,31 Elevated lipid accumulation in the liver is combined with fatty acid-induced gluconeogenesis and thereby with increased hepatic glucose production. 7,35 As during starvation, the liver is predominantly responsible for the maintenance of the blood glucose levels, and HepCL did not differ between candy-diet fed controls and rimonabant-treated , d), musculus extensor digitorum longus (EDL; b, e), and musculus tibialis (TIB; c, f) in the control chow group, control candy-diet group, rimonabant candy-diet group, as well as in the pair-fed group at the end of the treatment period.…”

Section: Discussionmentioning

confidence: 99%

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Reversal of visceral adiposity in candy-diet fed female Wistar rats by the CB1 receptor antagonist rimonabant

et al. 2008

Int J Obes

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Objective: The severity of obesity is often more determined by the distribution of fat depots rather than by body weight itself. Therefore, the effect of rimonabant on fat distribution pattern was investigated in female candy-fed Wistar rats. Design: Female Wistar rats were fed a high fat, high carbohydrate (candy-) diet for 12 weeks. During the last 6 weeks rats were treated with rimonabant. Food intake and body weight development were investigated, as well as effects on total body fat, especially visceral fat and ectopic lipid accumulation in skeletal muscle and liver, determined by in vivo magnetic resonance imaging/magnetic resonance spectroscopy. Results: Candy-diet increased body weight, which was predominantly due to the increased total fat mass with predominance of visceral fat accumulation. Treatment with rimonabant fully reversed the weight gain and fat deposition in the visceral cavity and skeletal muscle, in contrast to pair feeding. In spite of an only transient reduction of food intake, body weight reduction, as well as normalized body fat, reduced visceral fat and intramyocellular lipids were maintained over the treatment period. Conclusions: We conclude that additional factors other than reduced caloric intake must be responsible for the improvements in these lipid parameters. The complete cluster of results is consistent with increased lipid oxidation caused by rimonabant.

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Section: Discussionmentioning

confidence: 99%

“…Measurements of malonyl-CoA in muscle was performed in freeze-dried tissue, as described previously, whereas analysis of LCACoAs were slightly modified: 30,31 Tissue was homogenized and C17:0-CoA was added as an internal standard. LCACoAs were then extracted from the tissue.…”

Section: Analytical Procedures Of Blood Parametersmentioning

confidence: 99%

Reversal of visceral adiposity in candy-diet fed female Wistar rats by the CB1 receptor antagonist rimonabant

et al. 2008

Int J Obes

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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%

“…Neumann-Haefelin et al (7) showed that the increase in plasma free fatty acids (FFA) during starvation was paralleled by muscle-typedependent changes in IMCL content in the rat, when muscles were studied as a whole. To examine whether interventions with predicted increases in blood FFA (fasting and a high-fat diet) affected IMCL within the TA in a fiber-type-specific manner, we examined IMCL content after 15 hr of fasting and after consumption of a high-fat diet, and assessed its relation to muscle fiber typology.…”

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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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“…Indeed, current evidence suggests that when food is unavailable or intake is suspended (e.g., during migration in fish) for extended periods of time, lipids are preferentially oxidized over other fuel sources in both mammals and fish. In contrast, carbohydrates are spared to provide glucose to the brain and central nervous system (Neumann-Haefelin et al 2004), while proteins are usually oxidized as lipid stores decline (Frayn 1996). There are a host of metabolic modifications that must take place to increase lipid oxidation and decrease carbohydrate oxidation.…”

Section: Regulation Of Carnitine Palmitoyltransferase (Cpt) I During mentioning

confidence: 99%

Regulation of Carnitine Palmitoyltransferase (CPT) I during Fasting in Rainbow Trout (Oncorhynchus mykiss) Promotes Increased Mitochondrial Fatty Acid Oxidation

Morash

McClelland

2011

Physiological and Biochemical Zoology

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Periods of fasting, in most animals, are fueled principally by fatty acids, and changes in the regulation of fatty acid oxidation must exist to meet this change in metabolic substrate use. We examined the regulation of carnitine palmitoyltransferase (CPT) I, to help explain changes in mitochondrial fatty acid oxidation with fasting. After fasting rainbow trout (Oncorhynchus mykiss) for 5 wk, the mitochondria were isolated from red muscle and liver to determine (1) mitochondrial fatty acid oxidation rate, (2) CPT I activity and the concentration of malonyl-CoA needed to inhibit this activity by 50% (IC 50 ), (3) mitochondrial membrane fluidity, and (4) CPT I (all five known isoforms) and peroxisome proliferator-activated receptor (PPARa and PPARb) mRNA levels. Fatty acid oxidation in isolated mitochondria increased during fasting by 2.5-and 1.75-fold in liver and red muscle, respectively. Fasting also decreased sensitivity of CPT I to malonyl-CoA (increased IC 50 ), by two and eight times in red muscle and liver, respectively, suggesting it facilitates the rate of fatty acid oxidation. In the liver, there was also a significant increase CPT I activity per milligram mitochondrial protein and in whole-tissue PPARa and PPARb mRNA levels. However, there were no changes in mitochondrial membrane fluidity in either tissue, indicating that the decrease in CPT I sensitivity to malonyl-CoA is not due to bulk fluidity changes in the membrane. However, there were significant differences in CPT I mRNA levels during fasting. Overall, these data indicate some important changes in the regulation of CPT I that promote the increased mitochondrial fatty acid oxidation that occurs during fasting in trout.

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Muscle-Type Specific Intramyocellular and Hepatic Lipid Metabolism During Starvation in Wistar Rats

Cited by 28 publications

References 53 publications

Reversal of visceral adiposity in candy-diet fed female Wistar rats by the CB1 receptor antagonist rimonabant

Reversal of visceral adiposity in candy-diet fed female Wistar rats by the CB1 receptor antagonist rimonabant

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

Regulation of Carnitine Palmitoyltransferase (CPT) I during Fasting in Rainbow Trout (Oncorhynchus mykiss) Promotes Increased Mitochondrial Fatty Acid Oxidation

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