In addition to its anti-atherogenic role, HDL reportedly modulates energy metabolism at the whole-body level. HDL functionality is associated with its structure and composition, and functional activities can differ between HDL subclasses. Therefore, we studied if HDL2 and HDL3, the two major HDL subclasses, are able to modulate energy metabolism of skeletal muscle cells. Differentiated mouse and primary human skeletal muscle myotubes were used to investigate the influences of human HDL2 and HDL3 on glucose and fatty uptake and oxidation. HDL-induced changes in lipid distribution and mRNA expression of genes related to energy substrate metabolism, mitochondrial function and HDL receptors were studied with human myotubes. Additionally, we examined the effects of apoA-I and discoidal, reconstituted HDL particles (d-rHDLs) on substrate metabolism. In mouse myotubes, HDL subclasses strongly enhanced glycolysis upon high and low glucose concentrations. HDL3 caused a minor increase in ATP-linked respiration upon glucose conditioning but HDL2 improved complex I mediated mitochondrial respiration upon fatty acid treatment. In human myotubes, glucose metabolism was attenuated but fatty acid uptake and oxidation were markedly increased by both HDL subclasses, which also increased mRNA expression of genes related to fatty acid metabolism and HDL receptors. Finally, both HDL subclasses induced incorporation of oleic acid into different lipid classes. These results, demonstrating that HDL subclasses enhance fatty acid oxidation in human myotubes but improve anaerobic metabolism in mouse myotubes, support the role of HDL as a circulating modulator of energy metabolism. Exact mechanisms and components of HDL causing the change, require further investigation.

中文翻译：

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人类 HDL 亚类调节骨骼肌细胞的能量代谢。

据报道，除了抗动脉粥样硬化作用外，HDL 还能调节全身水平的能量代谢。HDL 功能与其结构和组成相关，HDL 子类之间的功能活动可能有所不同。因此，我们研究了 HDL2 和 HDL3 这两个主要 HDL 亚类是否能够调节骨骼肌细胞的能量代谢。使用分化的小鼠和原代人骨骼肌肌管来研究人 HDL2 和 HDL3 对葡萄糖和脂肪摄取和氧化的影响。利用人类肌管研究了 HDL 诱导的脂质分布变化以及与能量底物代谢、线粒体功能和 HDL 受体相关的基因 mRNA 表达的变化。此外，我们还研究了 apoA-I 和盘状重组 HDL 颗粒 (d-rHDL) 对底物代谢的影响。在小鼠肌管中，HDL 亚类在高和低葡萄糖浓度下强烈增强糖酵解。HDL3 在葡萄糖条件下引起 ATP 相关呼吸的轻微增加，但 HDL2 在脂肪酸处理后改善了复合物 I 介导的线粒体呼吸。在人类肌管中，两种HDL亚类的葡萄糖代谢减弱，但脂肪酸的摄取和氧化显着增加，这也增加了与脂肪酸代谢和HDL受体相关的基因的mRNA表达。最后，两个 HDL 亚类均诱导油酸掺入不同的脂质类别中。这些结果表明，HDL 亚类可增强人类肌管中的脂肪酸氧化，但可改善小鼠肌管中的无氧代谢，支持 HDL 作为能量代谢循环调节剂的作用。HDL 引起这种变化的确切机制和成分需要进一步研究。