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Autotaxin-Lysophosp...
Autotaxin-Lysophosphatidic Acid Signaling Contributed to Obesity-Induced Insulin Resistance in Muscle and Impairs Mitochondrial Metabolism
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- D'Souza, K. (author)
- Dalhousie Medicine New Brunswick, United States
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- Nzirorera, C. (author)
- Dalhousie Medicine New Brunswick, United States
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- Cowie, A.M. (author)
- Dalhousie Medicine New Brunswick, United States
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- Paramel Varghese, Geena, 1985- (author)
- Dalhousie Medicine New Brunswick, United States,Cardiovascular research center
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- Trivedi, P. (author)
- Dalhousie Medicine New Brunswick, United States
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- Eichmann, T.O. (author)
- Department of Biochemistry and Molecular Biology, Dalhousie University, Institute of Molecular Biosciences, Saint John, Canada
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- Biswas, D. (author)
- Dalhousie Medicine New Brunswick, United States
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- Touaibia, M. (author)
- University of Graz, Center for Explorative Lipidomics, BioTechMed-Graz, Department of Chemistry and Biochemistry, Graz, Austria
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- Morris, A.J. (author)
- Dalhousie Medicine New Brunswick, United States; Université de Moncton, Division of Cardiovascular Medicine, Moncton, Canada
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- Aidinis, V. (author)
- University of Kentucky, Lexington Veterans Affairs Medical Center, Division of Immunology, Lexington, United States
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- Kane, D.A. (author)
- Biomedical Sciences Research Center “Alexander Fleming”, Department of Human Kinetics, Athens, Greece
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- Pulinilkunnil, T. (author)
- Dalhousie Medicine New Brunswick, United States
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- Kienesberger, P.C. (author)
- Dalhousie Medicine New Brunswick, United States
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(creator_code:org_t)
- American Society for Biochemistry and Molecular Biology, 2018
- 2018
- English.
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In: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 59:10, s. 1805-1817
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https://oru.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- Metabolism
- insulin resistance
- Hälso- och sjukvårdsforskning
- Health and Medical Care Research
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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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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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
- Articles in the publication
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Journal of Lipid ...
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Örebro University