Resveratrol Blunts Mitochondrial Loss in Slow and Mixed Skeletal Muscle Phenotypes of Non-Human Primates following a Long-Term High Fat/Sugar Diet.
Resveratrol Blunts Mitochondrial Loss in Slow and Mixed Skeletal Muscle Phenotypes of Non-Human Primates following a Long-Term High Fat/Sugar Diet.
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DOI：
10.1080/19390211.2022.2039340
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发表时间：
2023
影响因子：
2.5
通讯作者：
Mattison, Julie A.
中科院分区：
文献类型：
--
作者：
Hyatt, Jon-Philippe K.;de Cabo, Rafael;Mattison, Julie A.
骨骼肌中的线粒体生物发生和破坏由不同的信号传导途径协调，所述信号传导途径受内部和外部变量的影响，所述变量包括但不限于肌肉表型、体力活动、饮食组成或药物施用。以前，我们发现长期白藜芦醇给药（高达480毫克/天）改善比目鱼肌的慢到快的表型转变，并促进非人灵长类动物消耗高脂肪/糖（HFS）饮食的混合跖肌中慢肌球蛋白重链的表达。在这里，我们通过检查线粒体含量和决定其生物发生和线粒体自噬/自噬的标志物是否同样受到HFS的影响和/或在食用这种饮食（HFSR）时受到白藜芦醇的影响来扩展这些早期的发现。与对照组（n=9）相比，HFS（n=8）肌肉中的线粒体含量减少约20-25%，如使用PCR分析的COX 2-和CYTB-与-GAPDH比率所反映的，其在HFSR（n=7）比目鱼肌中被白藜芦醇钝化，并且在跖肌中程度较低。与对照组相比，HFSR比目鱼肌和跖肌中的Rev-erb-α蛋白分别增加了约1.5倍和3倍。与HFSR动物不同，HFS比目鱼肌和跖肌磷酸化AMPK α（Thr 172）升高约2倍。HFS比目鱼肌磷酸化总TANK结合蛋白-1（TBK 1）的比率升高，表明线粒体/自噬事件增强。总的来说，白藜芦醇似乎通过缓和线粒体/自噬而不是促进线粒体生物合成来减弱高脂肪/糖饮食的线粒体损失，这表明每日摄入的白藜芦醇补充剂的量和/或其长期消费是重要的考虑因素。
Mitochondrial biogenesis and destruction in skeletal muscle are coordinated by distinct signaling pathways that are influenced by internal and exogenous variables including, but not limited to, muscle phenotype, physical activity, dietary composition, or drug administration. Previously we found that long-term resveratrol administration (up to 480 mg/day) ameliorates the slow-to-fast phenotypic shift in soleus muscles and promotes the expression in slow myosin heavy chain in the mixed plantaris muscle of non-human primates consuming a high fat/sugar (HFS) diet. Here, we expand on these earlier findings by examining whether mitochondrial content and the markers that dictate their biogenesis and mitophagy/autophagy are similarly affected by HFS and/or influenced by resveratrol while consuming this diet (HFSR). Compared to controls (n=9), there was a ~20–25% decrease in mitochondrial content in HFS (n=8) muscles as reflected in the COX2- and CYTB-to-GAPDH ratios using PCR analysis, which was blunted by resveratrol in HFSR (n=7) soleus and, to a lesser degree, in plantaris muscles. A ~1.5 and 3-fold increase in Rev-erb-α protein was detected in HFSR soleus and plantaris muscles compared to controls, respectively. Unlike in HFSR animals, HFS soleus and plantaris muscles exhibited a ~2-fold elevation in phosphor-AMPKα (Thr172). HFS soleus muscles had elevated phosphorylated-to-total TANK binding protein-1 (TBK1) ratio suggesting an enhancement in mito/autophagic events. Taken together, resveratrol appears to blunt mitochondrial losses with a high fat / sugar diet by tempering mito/autophagy rather than promoting mitochondrial biogenesis, suggesting that the quantity of daily resveratrol supplement ingested and / or its long-term consumption are important considerations.
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