Autotaxin-Lysophosphatidic Acid Signaling Contributed to Obesity-Induced Insulin Resistance in Muscle and Impairs Mitochondrial Metabolism [Elektronisk resurs]
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D'Souza, K. (författare)
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Nzirorera, C. (författare)
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Cowie, A.M. (författare)
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Paramel Varghese, Geena, 1985- (författare)
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Trivedi, P. (författare)
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Eichmann, T.O. (författare)
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Biswas, D. (författare)
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Touaibia, M. (författare)
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Morris, A.J. (författare)
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Aidinis, V. (författare)
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Kane, D.A. (författare)
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Pulinilkunnil, T. (författare)
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Kienesberger, P.C. (författare)
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Cardiovascular research center (medarbetare)
- Publicerad: American Society for Biochemistry and Molecular Biology, 2018
- Engelska.
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Ingår i: Journal of Lipid Research. - 0022-2275. ; 59:10, 1805-1817
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- Relaterad länk:
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http://www.oru.se/ (Värdpublikation)
Sammanfattning
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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.
Ämnesord
- Medical and Health Sciences (hsv)
- Medicin och hälsovetenskap (hsv)
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Physiology (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska och farmaceutiska grundvetenskaper (hsv)
- Fysiologi (hsv)
- Hälso- och sjukvårdsforskning (oru)
- Health and Medical Care Research (oru)
Genre
- government publication (marcgt)
Indexterm och SAB-rubrik
- Metabolism
- insulin resistance
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