1. Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo.
- Author
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Amengual J, García-Carrizo FJ, Arreguín A, Mušinović H, Granados N, Palou A, Bonet ML, and Ribot J
- Subjects
- AMP-Activated Protein Kinases metabolism, Animals, Cell Line, Enzyme-Linked Immunosorbent Assay, Fatty Acids metabolism, Fibroblast Growth Factors metabolism, Fibronectins blood, Fibronectins genetics, Glucose metabolism, Interleukin-6 metabolism, Lipid Metabolism drug effects, Liver drug effects, Liver metabolism, Liver pathology, Male, Mice, Muscle, Skeletal cytology, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Neuropeptides analysis, Neuropeptides metabolism, PPAR delta agonists, PPAR delta metabolism, PPAR-beta agonists, PPAR-beta metabolism, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism, Retinoid X Receptors agonists, Retinoid X Receptors metabolism, Triglycerides metabolism, Fibronectins metabolism, Tretinoin pharmacology
- Abstract
Background/aims: All-trans retinoic acid (ATRA) has protective effects against obesity and metabolic syndrome. We here aimed to gain further insight into the interaction of ATRA with skeletal muscle metabolism and secretory activity as important players in metabolic health., Methods: Cultured murine C2C12 myocytes were used to study direct effects of ATRA on cellular fatty acid oxidation (FAO) rate (using radioactively-labelled palmitate), glucose uptake (using radioactively-labelled 2-deoxy-D-glucose), triacylglycerol levels (by an enzymatic method), and the expression of genes related to FAO and glucose utilization (by RT-real time PCR). We also studied selected myokine production (using ELISA and immunohistochemistry) in ATRA-treated myocytes and intact mice., Results: Exposure of C2C12 myocytes to ATRA led to increased fatty acid consumption and decreased cellular triacylglycerol levels without affecting glucose uptake, and induced the expression of the myokine irisin at the mRNA and secreted protein level in a dose-response manner. ATRA stimulatory effects on FAO-related genes and the Fndc5 gene (encoding irisin) were reproduced by agonists of peroxisome proliferator-activated receptor β/δ and retinoid X receptors, but not of retinoic acid receptors, and were partially blocked by an AMP-dependent protein kinase inhibitor. Circulating irisin levels were increased by 5-fold in ATRA-treated mice, linked to increased Fndc5 transcription in liver and adipose tissues, rather than skeletal muscle. Immunohistochemistry analysis of FNDC5 suggested that ATRA treatment enhances the release of FNDC5/irisin from skeletal muscle and the liver and its accumulation in interscapular brown and inguinal white adipose depots., Conclusion: These results provide new mechanistic insights on how ATRA globally stimulates FAO and enhances irisin secretion, thereby contributing to leaning effects and improved metabolic status., (© 2018 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2018
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