Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Rd East, Guelph, ON, N1G 2W1, Canada.
Department of Health Sciences, Brock University, St Catharines, ON, Canada.
Diabetologia. 2018 Feb;61(2):433-444. doi: 10.1007/s00125-017-4456-3. Epub 2017 Oct 1.
AIMS/HYPOTHESIS: While the underlying mechanisms in the development of insulin resistance remain inconclusive, metabolic dysfunction in both white adipose tissue (WAT) and skeletal muscle have been implicated in the process. Therefore, we investigated the independent and combined effects of α-linolenic acid (ALA) supplementation and exercise training on whole-body glucose homeostasis and mitochondrial bioenergetics within the WAT and skeletal muscle of obese Zucker rats.
We randomly assigned obese Zucker rats to receive a control diet alone or supplemented with ALA and to remain sedentary or undergo exercise training for 4 weeks (CON-Sed, ALA-Sed, CON-Ex and ALA-Ex groups). Whole-body glucose tolerance was determined in response to a glucose load. Mitochondrial content and bioenergetics were examined in skeletal muscle and epididymal WAT (eWAT). Insulin sensitivity and cellular stress were assessed by western blot.
Exercise training independently improved whole-body glucose tolerance as well as insulin-induced signalling in muscle and WAT. However, the consumption of ALA during exercise training prevented exercise-mediated improvements in whole-body glucose tolerance. ALA consumption did not influence exercise-induced adaptations within skeletal muscle, insulin sensitivity and mitochondrial bioenergetics. In contrast, within eWAT, ALA supplementation attenuated insulin signalling, decreased mitochondrial respiration and increased the fraction of electron leak to reactive oxygen species (ROS).
CONCLUSIONS/INTERPRETATION: These findings indicate that, in an obese rodent model, consumption of ALA attenuates the favourable adaptive changes of exercise training within eWAT, which consequently impacts whole-body glucose homeostasis. The direct translation to humans, however, remains to be determined.
目的/假设：尽管胰岛素抵抗发展的潜在机制仍不明确，但白色脂肪组织（WAT）和骨骼肌中的代谢功能障碍已被牵涉到这一过程中。因此，我们研究了α-亚麻酸（ALA）补充和运动训练对肥胖 Zucker 大鼠全身葡萄糖稳态和 WAT 和骨骼肌中线粒体生物能学的独立和联合影响。
我们将肥胖 Zucker 大鼠随机分为单独接受对照饮食或补充 ALA 并保持久坐或进行 4 周运动训练的组（CON-Sed、ALA-Sed、CON-Ex 和 ALA-Ex 组）。通过葡萄糖负荷测定全身葡萄糖耐量。检查骨骼肌和附睾白色脂肪组织（eWAT）中的线粒体含量和生物能学。通过 Western blot 评估胰岛素敏感性和细胞应激。
运动训练独立改善了全身葡萄糖耐量以及肌肉和 WAT 中的胰岛素诱导信号。然而，在运动训练期间摄入 ALA 阻止了运动介导的全身葡萄糖耐量改善。ALA 消耗不影响骨骼肌、胰岛素敏感性和线粒体生物能学中的运动诱导适应性变化。相比之下，在 eWAT 中，ALA 补充减弱了胰岛素信号，降低了线粒体呼吸并增加了电子泄漏到活性氧（ROS）的比例。
结论/解释：这些发现表明，在肥胖啮齿动物模型中，ALA 的消耗减弱了 eWAT 中运动训练的有利适应性变化，从而影响全身葡萄糖稳态。然而，其直接转化为人类仍有待确定。
