Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
D'Souza, K; Nzirorera, C; Cowie, AM; Varghese, GP; Trivedi, P; Eichmann, TO; Biswas, D; Touaibia, M; Morris, AJ; Aidinis, V; Kane, DA; Pulinilkunnil, T; Kienesberger, PC.
Autotaxin-LPA signaling contributes to obesity-induced insulin resistance in muscle and impairs mitochondrial metabolism.
J Lipid Res. 2018; 59(10): 1805-1817.
Doi: 10.1194/jlr.M082008
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- Co-authors Med Uni Graz
- Eichmann Thomas
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Glucose - metabolism
- Homeostasis - administration & dosage
- Insulin - metabolism
- Insulin Resistance - administration & dosage
- Lysophospholipids - metabolism
- Mice - administration & dosage
- Mice, Inbred C57BL - administration & dosage
- Mitochondria - metabolism, pathology
- Muscle Fibers, Skeletal - metabolism, pathology
- Muscle, Skeletal - metabolism, pathology
- Obesity - metabolism, pathology
- Organ Specificity - administration & dosage
- Phosphoric Diester Hydrolases - metabolism
- Signal Transduction - administration & dosage
- Find related publications in this database (Keywords)
- diet effects/lipid metabolism
- glucose
- pyruvate
- skeletal muscle
- respiration