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首页> 外文期刊>Cellular Physiology and Biochemistry >Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo
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Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

机译：维甲酸增加骨骼肌细胞中脂肪酸的氧化和鸢尾素的表达，并影响鸢尾素的体内。

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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.
机译：背景/目的全反式维甲酸（ATRA）对肥胖和代谢综合征具有保护作用。我们的目标是进一步了解ATRA与骨骼肌代谢和分泌活性（在代谢健康中起重要作用）之间的相互作用。方法使用培养的鼠C2C12心肌细胞研究ATRA对细胞脂肪酸氧化（FAO）速率（使用放射性标记的棕榈酸酯），葡萄糖摄取（使用放射性标记的2-脱氧-D-葡萄糖），三酰甘油水平（通过（酶法）以及与FAO和葡萄糖利用有关的基因表达（通过RT-实时PCR）。我们还研究了经ATRA处理的心肌细胞和完整小鼠中选定的肌肉因子产生（使用ELISA和免疫组织化学）。结果C2C12心肌细胞暴露于ATRA导致脂肪酸消耗增加和细胞三酰甘油水平降低，而不会影响葡萄糖摄取，并以剂量​​反应方式诱导肌动蛋白虹膜素在mRNA的表达和分泌的蛋白水平。过氧化物酶体增殖物激活受体β/δ和类维生素A X受体的激动剂（而不是视黄酸受体）的激动剂复制了ATRA对FAO相关基因和Fndc5基因（编码鸢尾素）的刺激作用，但部分被AMP依赖性的阻断蛋白激酶抑制剂。在ATRA治疗的小鼠中，循环虹膜素水平增加了5倍，这与肝脏和脂肪组织（而非骨骼肌）中Fndc5转录的增加有关。 FNDC5的免疫组织化学分析表明，ATRA处理可增强FNDC5 / irisin从骨骼肌和肝脏的释放及其在肩inter间褐色和腹股沟白色脂肪贮藏库中的积累。结论这些结果为ATRA如何在全球范围内刺激FAO和增强虹膜素分泌提供了新的机制性见解，从而有助于倾斜效应和改善代谢状态。

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