Chronic AMP-activated protein kinase activation and a high-fat diet have an additive effect on mitochondria in rat skeletal muscle
Chronic AMP-activated protein kinase activation and a high-fat diet have an additive effect on mitochondria in rat skeletal muscle
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DOI：
10.1152/japplphysiol.00126.2010
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发表时间：
2010-08-01
影响因子：
3.3
通讯作者：
Hancock, Chad R.
中科院分区：
文献类型：
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作者：
Fillmore, Natasha;Jacobs, Daniel L.;Hancock, Chad R.
Fillmore N，Jacobs DL，米尔斯DB，Winder WW，汉考克CR.慢性AMP激活蛋白激酶激活和高脂饮食对大鼠骨骼肌线粒体有累加效应。J Appl Physiol 109：511-520，2010.首次发表于2010年6月3日; doi：10.1152/japplphysiol.00126.2010。刺激骨骼肌中线粒体生物发生的因素包括AMP活化蛋白激酶（AMPK）、钙和循环游离脂肪酸（FFA）。用5-氨基咪唑-4-甲酰胺核苷（AICAR）（AMPK的化学激活剂）或用高脂饮食增加循环FFA的慢性治疗增加了大鼠骨骼肌中的线粒体。本研究的目的是确定AMPK的慢性化学激活和高脂喂养的组合是否会对骨骼肌线粒体水平产生累加效应。我们用高脂饮食（HF）、AICAR注射液（AICAR）或高脂饮食和AICAR注射液（HF + AICAR）治疗Wistar雄性大鼠6周。在给药期结束时，在白色四头肌、红色四头肌和比目鱼肌中检查线粒体含量的标志物，这些肌肉主要由独特的肌纤维类型组成。在白色四头肌中，长链酰基辅酶A脱氢酶、细胞色素c和过氧化物酶体增殖物激活受体-γ共激活因子-1 α（PGC-1 α）蛋白以及柠檬酸合酶和β-羟酰基辅酶A脱氢酶（β-HAD）活性的处理具有累积效应。相反，在比目鱼肌中没有注意到加性效应，并且在红色四头肌中仅β-HAD活性增加。在白色股四头肌中观察到的线粒体标记物的累加增加可以通过两种单独机制的组合效应来解释：高脂饮食诱导的PGC-1 α蛋白的转录后增加和AMPK介导的PGC-1 α蛋白通过转录机制的增加。这些数据表明，AMPK的慢性化学活化和高脂饮食对脂肪酸氧化、柠檬酸循环、电子传递链和转录调控的标志物具有肌肉类型特异性加和效应。
Fillmore N, Jacobs DL, Mills DB, Winder WW, Hancock CR. Chronic AMP-activated protein kinase activation and a high-fat diet have an additive effect on mitochondria in rat skeletal muscle. J Appl Physiol 109: 511-520, 2010. First published June 3, 2010; doi: 10.1152/japplphysiol.00126.2010.-Factors that stimulate mitochondrial biogenesis in skeletal muscle include AMP-activated protein kinase (AMPK), calcium, and circulating free fatty acids (FFAs). Chronic treatment with either 5-aminoimidazole-4-carboxamide riboside (AICAR), a chemical activator of AMPK, or increasing circulating FFAs with a high-fat diet increases mitochondria in rat skeletal muscle. The purpose of this study was to determine whether the combination of chronic chemical activation of AMPK and high-fat feeding would have an additive effect on skeletal muscle mitochondria levels. We treated Wistar male rats with a high-fat diet (HF), AICAR injections (AICAR), or a high-fat diet and AICAR injections (HF + AICAR) for 6 wk. At the end of the treatment period, markers of mitochondrial content were examined in white quadriceps, red quadriceps, and soleus muscles, predominantly composed of unique muscle-fiber types. In white quadriceps, there was a cumulative effect of treatments on long-chain acyl-CoA dehydrogenase, cytochrome c, and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) protein, as well as on citrate synthase and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD) activity. In contrast, no additive effect was noted in the soleus, and in the red quadriceps only beta-HAD activity increased additively. The additive increase of mitochondrial markers observed in the white quadriceps may be explained by a combined effect of two separate mechanisms: high-fat diet-induced posttranscriptional increase in PGC-1 alpha protein and AMPK-mediated increase in PGC-1 alpha protein via a transcriptional mechanism. These data show that chronic chemical activation of AMPK and a high-fat diet have a muscle type specific additive effect on markers of fatty acid oxidation, the citric acid cycle, the electron transport chain, and transcriptional regulation.