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Resveratrol‐induced remodelling of myocellular lipid stores: A study in metabolically compromised humans

机译：白藜芦醇诱导的肌细胞脂质储备的重塑：代谢受损人类的研究

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Abstract In non‐athletes, insulin sensitivity correlates negatively with intramyocellular lipid (IMCL) content. In athletes, however, a pattern of benign IMCL storage exists, which is characterized by lipid storage in type I muscle fibres, in small and numerous lipid droplets (LDs) preferable coated with PLIN5, without affecting insulin sensitivity. Administration of resveratrol has been promoted for its beneficial effects on glucose homeostasis. We observed that 30 days of oral resveratrol administration (150 mg/day) in metabolically compromised individuals showed a 33% increase in IMCL (placebo vs. resveratrol; 0.86 ± 0.090 AU vs. 1.14 ± 0.11 AU, p = 0.003) without impeding insulin sensitivity. Thus, the aim of the present study was to examine if a resveratrol‐mediated increase in IMCL content, in metabolically compromised individuals, changes the LD phenotype towards the phenotype we previously observed in athletes. For this, we studied IMCL, LD number, LD size, subcellular distribution and PLIN5 coating in different fibre types using high‐resolution confocal microscopy. As proof of concept, we observed a 2.3‐fold increase (p = 0.038) in lipid accumulation after 48 h of resveratrol incubation in cultured human primary muscle cells. In vivo analysis showed that resveratrol‐induced increase in IMCL is predominantly in type I muscle fibres (placebo vs. resveratrol; 0.97 ± 0.16% vs. 1.26 ± 0.09%; p = 0.030) in both the subsarcolemmal (p = 0.016) and intermyofibrillar region (p = 0.026) and particularly in PLIN5‐coated LDs (p = 0.024). These data indicate that administration of resveratrol augments IMCL content in metabolically compromised individuals towards a LD phenotype that mimics an ‘athlete like phenotype’.
机译：摘要在非运动员中，胰岛素敏感性与脑内脂质（IMCL）含量负相关。然而，在运动员中，存在一种良性IMCL储存的模式，其特征在于I型肌肉纤维中的脂质储存，其中含有PLIN5的小和许多脂质液滴（LDS），而不影响胰岛素敏感性。已促进白藜芦醇的施用对其对葡萄糖稳态的有益作用。我们观察到，在代谢受损的个体口服施用白藜芦醇（150毫克/天）30天显示出增加IMCL 33％（安慰剂对比白藜芦醇; 0.86±0.090 AU与1.14±0.11 AU，p值= 0.003），而不会阻碍胰岛素灵敏度。因此，本研究的目的是检查是否在IMCL含量白藜芦醇介导的增加，代谢受损的个体，对改变我们以前在运动员中观察到的表型的LD表型。为此，我们使用高分辨率共聚焦显微镜研究了不同纤维类型的IMCL，LD号，LD尺寸，亚细胞分布和PLIN5涂层。作为概念证明，我们观察到培养的人原肌细胞中的白藜芦醇孵育48小时后，观察到2.3倍的脂质积累中的脂质积累。体内分析表明在IMCL，白藜芦醇诱导的增加主要是在I型肌纤维（安慰剂与白藜芦醇; 0.97±0.16％比1.26±0.09％; P = 0.030）中均肌膜（P = 0.016）和intermyofibrillar区域（P = 0.026），特别是在PLIN5涂覆的LDS中（P = 0.024）。这些数据表明，白藜芦醇给予IMCL含量在代谢地受损的个体中朝向模拟“运动员等表型”的LD表型。

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