Retinoic acid exerts sexually dimorphic effects on muscle energy metabolism and function.
Retinoic acid exerts sexually dimorphic effects on muscle energy metabolism and function.
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DOI：
10.1016/j.jbc.2021.101101
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Napoli JL
中科院分区：
文献类型：
--
作者：
Zhao Y;Vuckovic M;Yoo HS;Fox N;Rodriguez A;McKessy K;Napoli JL
视黄醇脱氢酶Rdh10催化限速反应，将视黄醇转化为维甲酸(RA)，维甲酸是一种调节能量平衡和降低肥胖症的金盏花。骨骼肌消耗的能量几乎是普通人的一半，有助于预防肥胖。我们报道了Rdh10+/−小鼠在能量代谢和肌肉功能方面的性别差异。与野生型(WT)对照组相比，喂食高脂肪饮食的RDH10+/−男性减少了对脂肪酸氧化的依赖，并经历了葡萄糖耐量和胰岛素抵抗。跑步耐力下降40%。喂食这种饮食的Rdh10+/−女性增加了脂肪酸氧化，并且既没有葡萄糖耐受不良，也没有胰岛素抵抗。跑步耐力提高220%。因此，我们评估了混合纤维型腓肠肌(GM)的RA功能，这种肌肉有助于跑步，而不是站立，并且类似于人类GM。RDH10+/−男性GM组RA水平较WT组下降38%。Rdh10+/−雄性GM增加MYOG的表达，降低Eif6mRNAs的表达，从而降低和提高跑步耐力。Cox5A、复合体IV活性和ATP活性降低。集中核团的增多表明GM纤维中存在肌肉疾病和/或修复。相比之下，Rdh10+/−女性GM的RA下降不到男性下降的一半，而Rdh10的下降较为温和，雌激素诱导的视黄醇脱氢酶Dhrs9增加。Myog基因表达下降。Cox5A、复合体IV活性和ATP活性增加。集中的GM核不会增加。我们得出结论，Rdh10/RA部分通过对骨骼肌基因表达、结构和线粒体活性的性别二态效应影响全身能量消耗和胰岛素抵抗。
The retinol dehydrogenase Rdh10 catalyzes the rate-limiting reaction that converts retinol into retinoic acid (RA), an autacoid that regulates energy balance and reduces adiposity. Skeletal muscle contributes to preventing adiposity, by consuming nearly half the energy of a typical human. We report sexually dimorphic differences in energy metabolism and muscle function in Rdh10+/− mice. Relative to wild-type (WT) controls, Rdh10+/− males fed a high-fat diet decrease reliance on fatty-acid oxidation and experience glucose intolerance and insulin resistance. Running endurance decreases 40%. Rdh10+/− females fed this diet increase fatty acid oxidation and experience neither glucose intolerance nor insulin resistance. Running endurance increases 220%. We therefore assessed RA function in the mixed-fiber type gastrocnemius muscles (GM), which contribute to running, rather than standing, and are similar to human GM. RA levels in Rdh10+/− male GM decrease 38% relative to WT. Rdh10+/− male GM increase expression of Myog and reduce Eif6 mRNAs, which reduce and enhance running endurance, respectively. Cox5A, complex IV activity, and ATP decrease. Increased centralized nuclei reveal existence of muscle malady and/or repair in GM fibers. Comparatively, RA in Rdh10+/− female GM decreases by less than half the male decrease, from a more modest decrease in Rdh10 and an increase in the estrogen-induced retinol dehydrogenase Dhrs9. Myog mRNA decreases. Cox5A, complex IV activity, and ATP increase. Centralized GM nuclei do not increase. We conclude that Rdh10/RA affects whole body energy use and insulin resistance partially through sexual dimorphic effects on skeletal muscle gene expression, structure, and mitochondria activity.
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影响因子：
4.8
作者：
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STANCEL, GM
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2.7
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