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Autotaxin-Lysophosp...
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D'Souza, K.Dalhousie Medicine New Brunswick, United States
(författare)
Autotaxin-Lysophosphatidic Acid Signaling Contributed to Obesity-Induced Insulin Resistance in Muscle and Impairs Mitochondrial Metabolism
- Artikel/kapitelEngelska2018
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American Society for Biochemistry and Molecular Biology,2018
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:oru-71323
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-71323URI
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https://doi.org/10.1194/jlr.M082008DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding Agencies:Natural Sciences and Engineering Research Council of Canada Canadian Institutes of Health Research Project Banting Research Foundation New Brunswick Health Research Foundation New Brunswick Innovation Foundation Heart and Stroke Foundation of CanadaNatural Sciences and Engineering Research Council of CanadaCanadian Diabetes Association Canada Foundation for Innovation
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Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid (LPA). ATX-LPA signaling has been implicated in diet-induced obesity and systemic insulin resistance. However, it remains unclear whether the ATX-LPA pathway influences insulin function and energy metabolism in target tissues, particularly skeletal muscle, the major site of insulin-stimulated glucose disposal. The objective of this study was to test whether the ATX-LPA pathway impacts tissue insulin signaling and mitochondrial metabolism in skeletal muscle during obesity. Male mice with heterozygous ATX deficiency (ATX +/-) were protected from obesity, systemic insulin resistance, and cardiomyocyte dysfunction following high-fat high-sucrose (HFHS) feeding. HFHS-fed ATX +/- mice also had improved insulin-stimulated AKT phosphorylation in white adipose tissue, liver, heart, and skeletal muscle. Preserved insulin-stimulated glucose transport in muscle from HFHS fed ATX +/- mice was associated with improved mitochondrial pyruvate oxidation in the absence of changes in fat oxidation and ectopic lipid accumulation. Similarly, incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function. Preserved insulin-stimulated glucose transport in muscle from HFHS fed ATX +/- mice was associated with improved mitochondrial pyruvate oxidation in the absence of changes in fat oxidation and ectopic lipid accumulation. Similarly, incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function. Preserved insulin-stimulated glucose transport in muscle from HFHS fed ATX +/- mice was associated with improved mitochondrial pyruvate oxidation in the absence of changes in fat oxidation and ectopic lipid accumulation. Similarly, incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function. incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function. incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Nzirorera, C.Dalhousie Medicine New Brunswick, United States
(författare)
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Cowie, A.M.Dalhousie Medicine New Brunswick, United States
(författare)
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Paramel Varghese, Geena,1985-Dalhousie Medicine New Brunswick, United States,Cardiovascular research center(Swepub:oru)gpl
(författare)
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Trivedi, P.Dalhousie Medicine New Brunswick, United States
(författare)
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Eichmann, T.O.Department of Biochemistry and Molecular Biology, Dalhousie University, Institute of Molecular Biosciences, Saint John, Canada
(författare)
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Biswas, D.Dalhousie Medicine New Brunswick, United States
(författare)
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Touaibia, M.University of Graz, Center for Explorative Lipidomics, BioTechMed-Graz, Department of Chemistry and Biochemistry, Graz, Austria
(författare)
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Morris, A.J.Dalhousie Medicine New Brunswick, United States; Université de Moncton, Division of Cardiovascular Medicine, Moncton, Canada
(författare)
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Aidinis, V.University of Kentucky, Lexington Veterans Affairs Medical Center, Division of Immunology, Lexington, United States
(författare)
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Kane, D.A.Biomedical Sciences Research Center “Alexander Fleming”, Department of Human Kinetics, Athens, Greece
(författare)
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Pulinilkunnil, T.Dalhousie Medicine New Brunswick, United States
(författare)
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Kienesberger, P.C.Dalhousie Medicine New Brunswick, United States
(författare)
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Dalhousie Medicine New Brunswick, United StatesCardiovascular research center
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Lipid Research: American Society for Biochemistry and Molecular Biology59:10, s. 1805-18170022-22751539-7262
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D'Souza, K.
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Nzirorera, C.
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Cowie, A.M.
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Paramel Varghese ...
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Trivedi, P.
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Eichmann, T.O.
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visa fler...
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Biswas, D.
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Touaibia, M.
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Morris, A.J.
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Aidinis, V.
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Kane, D.A.
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Pulinilkunnil, T ...
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Kienesberger, P. ...
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