Muscle type-specific fatty acid metabolism in insulin resistance: an integrated in vivo study in Zucker diabetic fatty rats

Beha, Anja; Juretschke, Hans-Paul; Kuhlmann, Johanna; Neumann-Haefelin, Claudia; Belz, Ulrich; Gerl, Martin; Kramer, Werner; Roden, Michael; Herling, Andreas W.

doi:10.1152/ajpendo.00459.2005

Cited by 25 publications

(28 citation statements)

References 64 publications

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“…Exploitation of alternate pathways of glucose uptake could be valuable in treating disorders with impaired insulinmediated uptake. Our C 2 /LPL myoblasts have some characteristics reported previously in insulin-resistant states such as increased myocellular lipid accumulation, increased non-insulin-mediated glucose uptake (4,10,18), decreased Akt phosphorylation (2, 46), and decreased hexokinase II expression (5,34). Intracellular lipid accumulation with concurrent increased glucose uptake is also a characteristic reported in cancer cell models (26).…”

Section: Discussionsupporting

confidence: 52%

Fatty acids increase glucose uptake and metabolism in C₂C₁₂myoblasts stably transfected with human lipoprotein lipase

Capell

Schlaepfer

Wolfe³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Capell WH, Schlaepfer IR, Wolfe P, Watson PA, Bessesen DH, Pagliassotti MJ, Eckel RH. Fatty acids increase glucose uptake and metabolism in C2C12 myoblasts stably transfected with human lipoprotein lipase. Am J Physiol Endocrinol Metab 299: E576 -E583, 2010. First published July 13, 2010; doi:10.1152/ajpendo.00618.2009.-Cellular effects of FFA might differ from those of lipoprotein triglyceride (TG)-derived fatty acids (TGFA). The aim of the current study was to examine the relationship between lipoprotein lipase (LPL) expression, TGFA, or FFA availability and glucose metabolism in the absence of insulin in C 2C12 myoblasts. Control myoblasts or myoblasts stably transfected with human lipoprotein lipase (C2/LPL; 15-fold greater LPL activity) were incubated for 12 h in fetal bovine serum-free medium in the absence or presence of Intralipid-20. Intracellular retention of labeled medium glucose was assessed in a subset of experiments. In the presence of Intralipid, medium glucose disappearance was increased in C2/LPL cells but not in control cells. In both cell types, glucose label retention in cellular TG was increased in the presence of Intralipid; incubation with albumin-bound oleate produced similar results. In the presence of Intralipid, the LPL hydrolytic inhibitor tetrahydrolipstatin blocked excess glucose retention in cellular TG but did not significantly decrease glucose disappearance in C2/LPL cells. Changes in glucose transport or hexokinase II did not explain the altered glucose disappearance in C2/LPL cells. Our results suggest that LPL overexpression in these cells leads to chronic metabolic adaptations that alter glucose uptake and retention. in vitro; intracellular lipid; Akt; AMP-activated protein kinase; glucose transporter FATTY ACIDS AND GLUCOSE CAN COMPETE as oxidative fuels within muscle [for review, see Randle (37)]. Additionally, increased triglyceride (TG) content has been associated with insulin resistance in various insulin-sensitive tissues (21,24,29,31,41,43), and accumulation of lipid species within cells might directly affect cell insulin signaling (42). Therefore, examining cellular interactions between lipid and glucose may be valuable in understanding cell metabolism and the pathogenesis of insulin resistance.Studies of the cellular effects of lipids typically focus on free fatty acids (FFA) and have only rarely examined lipoprotein TG-derived fatty acids (TGFA). Circulating within lipoproteins, TGFA have the potential for unique cellular interactions that are distinct from FFA. Specifically, TGFA enter skeletal muscle cells and adipocytes following hydrolytic release, requiring the hydrolytic enzyme lipoprotein lipase (LPL) (14). Additionally, the binding of lipoproteins to LPL at the endothelial surface allows lipoproteins to interact with cell receptors and promotes whole particle uptake (6,13,28,38). Most studies to date utilizing TG emulsions have coinfused heparin, which releases LPL from its endothelial-bound position and disrupts these potential bridging functions. Because ...

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Section: Discussionsupporting

confidence: 52%

Fatty acids increase glucose uptake and metabolism in C₂C₁₂myoblasts stably transfected with human lipoprotein lipase

Capell

Schlaepfer

Wolfe³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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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%

“…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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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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“…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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Muscle type-specific fatty acid metabolism in insulin resistance: an integrated in vivo study in Zucker diabetic fatty rats

Abstract: . Muscle-type specific fatty acid metabolism in insulin resistance: an integrated in vivo study in Zucker diabetic fatty rats.

Cited by 25 publications

References 64 publications

Fatty acids increase glucose uptake and metabolism in C₂C₁₂myoblasts stably transfected with human lipoprotein lipase

Fatty acids increase glucose uptake and metabolism in C₂C₁₂myoblasts stably transfected with human lipoprotein lipase

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

Role of proton MR for the study of muscle lipid metabolism

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Muscle type-specific fatty acid metabolism in insulin resistance: an integrated in vivo study in Zucker diabetic fatty rats

Abstract: . Muscle-type specific fatty acid metabolism in insulin resistance: an integrated in vivo study in Zucker diabetic fatty rats.

Cited by 25 publications

References 64 publications

Fatty acids increase glucose uptake and metabolism in C2C12myoblasts stably transfected with human lipoprotein lipase

Fatty acids increase glucose uptake and metabolism in C2C12myoblasts stably transfected with human lipoprotein lipase

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

Role of proton MR for the study of muscle lipid metabolism

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Fatty acids increase glucose uptake and metabolism in C₂C₁₂myoblasts stably transfected with human lipoprotein lipase

Fatty acids increase glucose uptake and metabolism in C₂C₁₂myoblasts stably transfected with human lipoprotein lipase