Dept. of Human Health and Nutritional Sciences, Animal Science and Nutrition Bldg., Rm 205, University of Guelph, Guelph, ON, Canada.
Am J Physiol Regul Integr Comp Physiol. 2011 Feb;300(2):R492-500. doi: 10.1152/ajpregu.00602.2010. Epub 2010 Nov 17.
Leptin administration increases fatty acid (FA) oxidation rates and decreases lipid storage in oxidative skeletal muscle, thereby improving insulin response. We have previously shown high-fat (HF) diets to rapidly induce skeletal muscle leptin resistance, prior to the disruption of normal muscle FA metabolism (increase in FA transport; accumulation of triacylglycerol, diacylglycerol, ceramide) that occurs in advance of impaired insulin signaling and glucose transport. All of this occurs within a 4-wk period. Conversely, exercise can rapidly improve insulin response, in as little as one exercise bout. Thus, if the early development of leptin resistance is a contributor to HF diet-induced insulin resistance (IR) in skeletal muscle, then it is logical to predict that the rapid restoration of insulin response by exercise training would be preceded by the recovery of leptin response. In the current study, we sought to determine 1) whether 1, 2, or 4 wk of exercise training was sufficient to restore leptin response in isolated soleus muscle of rats already consuming a HF diet (60% kcal), and 2) whether this preceded the training-induced corrections in FA metabolism and improved insulin-stimulated glucose transport. In the low-fat (LF)-fed control group, insulin increased glucose transport by 153% and leptin increased AMPK and ACC phosphorylation and the rate of palmitate oxidation (+73%). These responses to insulin and leptin were either severely blunted or absent following 4 wk of HF feeding. Exercise intervention decreased muscle ceramide content (-28%) and restored insulin-stimulated glucose transport to control levels within 1 wk; muscle leptin response (AMPK and ACC phosphorylation, FA oxidation) was also restored, but not until the 2-wk time point. In conclusion, endurance exercise training is able to restore leptin response, but this does not appear to be a necessary precursor for the restoration of insulin response.
瘦素（Leptin）的作用是增加脂肪酸（FA）的氧化速率，减少脂肪在氧化型骨骼肌中的储存，从而改善胰岛素的反应。我们之前的研究表明，高脂肪（HF）饮食会迅速导致骨骼肌对瘦素产生抵抗，这先于正常肌肉 FA 代谢的破坏（FA 转运增加；三酰甘油、二酰甘油和神经酰胺的积累），而后者又先于胰岛素信号和葡萄糖转运受损。所有这些都在 4 周内发生。相反，运动可以在短短一次运动过程中迅速改善胰岛素的反应。因此，如果瘦素抵抗的早期发展是 HF 饮食引起骨骼肌胰岛素抵抗（IR）的一个因素，那么可以合理地预测，运动训练迅速恢复胰岛素反应，将先于瘦素反应的恢复。在目前的研究中，我们试图确定 1）1、2 或 4 周的运动训练是否足以恢复已经摄入 HF 饮食（60%卡路里）的大鼠的孤立比目鱼肌的瘦素反应，2）这是否先于训练引起的 FA 代谢纠正和改善胰岛素刺激的葡萄糖转运。在低脂（LF）喂养的对照组中，胰岛素使葡萄糖转运增加了 153%，瘦素增加了 AMPK 和 ACC 磷酸化以及棕榈酸氧化率（+73%）。在 HF 喂养 4 周后，这些对胰岛素和瘦素的反应要么严重减弱，要么完全消失。运动干预降低了肌肉神经酰胺含量（-28%），并在 1 周内将胰岛素刺激的葡萄糖转运恢复到对照水平；肌肉瘦素反应（AMPK 和 ACC 磷酸化，FA 氧化）也得到了恢复，但直到 2 周时才恢复。总之，耐力运动训练能够恢复瘦素反应，但这似乎不是恢复胰岛素反应的必要前提。
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