Williams Cameron B, Hughes Meghan C, Edgett Brittany A, Scribbans Trisha D, Simpson Craig A, Perry Christopher G R, Gurd Brendon J
School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.
School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
PLoS One. 2014 Jul 14;9(7):e102406. doi: 10.1371/journal.pone.0102406. eCollection 2014.
The current study tested the hypothesis that a single, moderate dose of RSV would activate the AMPK/SIRT1 axis in human skeletal muscle and adipose tissue. Additionally, the effects of RSV on mitochondrial respiration in PmFBs were examined. Eight sedentary men (23.8±2.4 yrs; BMI: 32.7±7.1) reported to the lab on two occasions where they were provided a meal supplemented with 300 mg of RSV or a placebo. Blood samples, and a muscle biopsy were obtained in the fasted state and again, with the addition of an adipose tissue biopsy, two hours post-prandial. The effect of RSV on mitochondrial respiration was examined in PmFBs taken from muscle biopsies from an additional eight men (23.4±5.4 yrs; BMI: 24.4±2.8). No effect of RSV was observed on nuclear SIRT1 activity, acetylation of p53, or phosphorylation of AMPK, ACC or PKA in either skeletal muscle or adipose tissue. A decrease in post absorptive insulin levels was accompanied by elevated skeletal muscle phosphorylation of p38 MAPK, but no change in either skeletal muscle or adipose tissue insulin signalling. Mitochondrial respiration in PmFBs was rapidly inhibited by RSV at 100-300 uM depending on the substrate examined. These results question the efficacy of a single dose of RSV at altering skeletal muscle and adipose tissue AMPK/SIRT1 activity in humans and suggest that RSV mechanisms of action in humans may be associated with altered cellular energetics resulting from impaired mitochondrial ATP production.
单次中等剂量的白藜芦醇（RSV）会激活人体骨骼肌和脂肪组织中的AMPK/SIRT1轴。此外，还研究了RSV对人前脂肪细胞（PmFBs）线粒体呼吸的影响。八名久坐不动的男性（23.8±2.4岁；体重指数：32.7±7.1）分两次到实验室，每次分别给予他们一顿补充了300毫克RSV的餐食或安慰剂。在空腹状态下采集血样和肌肉活检样本，餐后两小时再次采集，同时增加脂肪组织活检样本。从另外八名男性（23.4±5.4岁；体重指数：24.4±2.8）的肌肉活检样本中获取PmFBs，研究RSV对线粒体呼吸的影响。未观察到RSV对骨骼肌或脂肪组织中的核SIRT1活性、p53乙酰化或AMPK、ACC或PKA磷酸化有任何影响。吸收后胰岛素水平降低，同时骨骼肌中p38丝裂原活化蛋白激酶（p38 MAPK）磷酸化水平升高，但骨骼肌或脂肪组织中的胰岛素信号均无变化。根据所检测的底物不同，100 - 300微摩尔的RSV可迅速抑制PmFBs中的线粒体呼吸。这些结果对单次剂量RSV改变人体骨骼肌和脂肪组织中AMPK/SIRT1活性的功效提出了质疑，并表明RSV在人体中的作用机制可能与线粒体ATP生成受损导致的细胞能量代谢改变有关。
