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  • High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle.

High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle.

Endocrinology (2013-03-09)
Pierre-Marie Badin, Isabelle K Vila, Katie Louche, Aline Mairal, Marie-Adeline Marques, Virginie Bourlier, Geneviève Tavernier, Dominique Langin, Cedric Moro
ZUSAMMENFASSUNG

Elevated expression/activity of adipose triglyceride lipase (ATGL) and/or reduced activity of hormone-sensitive lipase (HSL) in skeletal muscle are causally linked to insulin resistance in vitro. We investigated here the effect of high-fat feeding on skeletal muscle lipolytic proteins, lipotoxicity, and insulin signaling in vivo. Five-week-old C3H mice were fed normal chow diet (NCD) or 45% kcal high-fat diet (HFD) for 4 weeks. Wild-type and HSL knockout mice fed NCD were also studied. Whole-body and muscle insulin sensitivity, as well as lipolytic protein expression, lipid levels, and insulin signaling in skeletal muscle, were measured. HFD induced whole-body insulin resistance and glucose intolerance and reduced skeletal muscle glucose uptake compared with NCD. HFD increased skeletal muscle total diacylglycerol (DAG) content, protein kinase Cθ and protein kinase Cε membrane translocation, and impaired insulin signaling as reflected by a robust increase of basal Ser1101 insulin receptor substrate 1 phosphorylation (2.8-fold, P < .05) and a decrease of insulin-stimulated v-Akt murine thymoma viral oncogene homolog Ser473 (-37%, P < .05) and AS160 Thr642 (-47%, P <.01) phosphorylation. We next showed that HFD strongly reduced HSL phosphorylation at Ser660. HFD significantly up-regulated the muscle protein content of the ATGL coactivator comparative gene identification 58 and triacylglycerol hydrolase activity, despite a lower ATGL protein content. We further show a defective skeletal muscle insulin signaling and DAG accumulation in HSL knockout compared with wild-type mice. Together, these data suggest a pathophysiological link between altered skeletal muscle lipase expression and DAG-mediated insulin resistance in mice.

MATERIALIEN
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Produktbeschreibung

Sigma-Aldrich
Lipase aus Candida rugosa, Type VII, ≥700 unit/mg solid
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Lipase aus Schweinepankreas, Type II, ≥125 units/mg protein (using olive oil (30 min incubation)), 30-90 units/mg protein (using triacetin)
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Lipase-Acrylharz aus Candida antarctica, ≥5,000 U/g, recombinant, expressed in Aspergillus niger
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Esterase aus Schweineleber, lyophilized powder, ≥15 units/mg solid
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Lipase aus Schweinepankreas, Type VI-S, ≥20,000 units/mg protein, lyophilized powder
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Lipase B Candida antarctica, rekombinant aus Aspergillus oryzae, powder, beige, ~9 U/mg
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Lipase aus Aspergillus niger, powder (fine), ~200 U/g
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Lipase aus Aspergillus oryzae, solution, ≥100,000 U/g, white, beige
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Lipase aus Candida rugosa, lyophilized powder, ≥40,000 units/mg protein
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Esterase aus Schweineleber, ammonium sulfate suspension, ≥150 units/mg protein (biuret)
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Lipase, immobilisiert aus Candida antarctica, beads, slightly brown, >2 U/mg
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Lipase aus Candida sp., recombinant, expressed in Aspergillus niger
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Lipase aus Pseudomonas cepacia, powder, light beige, ≥30 U/mg
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Lipase aus Rhizomucor miehei, ≥20,000 U/g
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Lipase aus Weizenkeimen, Type I, lyophilized powder, 5-15 units/mg solid
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Esterase aus Bacillus subtilis, recombinant, expressed in E. coli, ≥10 U/mg
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Lipase aus Rhizopus oryzae, powder (fine), ~10 U/mg
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Esterase aus Schweineleber, lyophilized, powder, slightly beige, ≥50 U/mg
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Lipase aus Aspergillus oryzae, lyophilized, powder, white, ~50 U/mg
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Lipase aus Pseudomonas sp., Type XIII, lyophilized powder, ≥15 units/mg solid
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Lipase aus Candida rugosa, lyophilized, powder (fine), 15-25 U/mg
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Carboxylesterase 1 isoform b human, recombinant, expressed in baculovirus infected BTI insect cells
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Lipase aus Candida rugosa, powder, yellow-brown, ≥2 U/mg
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Lipase aus Mucor miehei, lyophilized powder, ≥4,000 units/mg solid (using olive oil)
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Esterase aus Kaninchenleber, lyophilized powder, ≥30 units/mg protein
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Esterase aus Bacillus stearothermophilus, recombinant, expressed in E. coli, ≥4.0 U/mg
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Esterase aus Bacillus stearothermophilus, ≥0.2 U/mg
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Lipase aus Mucor miehei, powder, slightly brown, ~1 U/mg
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Carboxylesterase 2 human, recombinant, expressed in mouse NSO cells, ≥95% (SDS-PAGE)
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Lipase aus Rhizopus niveus, powder (fine), ≥1.5 U/mg