Department of Agriculture, Food and Nutritional Sciences, University of Alberta, Edmonton, Alberta, Canada.
PLoS One. 2012;7(7):e41719. doi: 10.1371/journal.pone.0041719. Epub 2012 Jul 23.
Glyceroneogenesis is an important step in the control of fatty acid re-esterification with PEPCK and PDK4 being identified as key enzymes in this process. We have previously shown that glyceroneogenic enzymes such as PDK4 are rapidly induced in white adipose tissue during exercise. Recent studies have suggested that IL-6 regulates adipose tissue metabolism and gene expression during exercise. Interestingly, IL-6 has been reported to directly decrease PEPCK expression. The purpose of this investigation was to determine the role of IL-6 in modulating the effects of exercise on the expression of glyceroneogenic enzymes in mouse adipose tissue. We hypothesized that the exercise-mediated induction of PDK4 and PEPCK would be greater in adipose tissue from IL-6 deficient mice compared to wild type controls.
Treatment of cultured epididymal adipose tissue (eWAT) with IL-6 (150 ng/ml) increased the phosphorylation of AMPK, ACC and STAT3 and induced SOCS3 mRNA levels while decreasing PEPCK and PDK4 mRNA. AICAR decreased the expression of PDK4 and PEPCK. The activation of AMPK by IL-6 was independent of increases in lipolysis. An acute bout of treadmill running (15 meters/minute, 5% incline, 90 minutes) did not induce SOCS3 or increase phosphorylation of STAT3 in eWAT, indicating that IL-6 signalling was not activated. Exercise-induced increases in PEPCK and PDK4 mRNA expression were attenuated in eWAT from IL-6(-/-) mice in parallel with a greater relative increase in AMPK phosphorylation compared to exercised WT mice. These changes occurred independent of alterations in beta-adrenergic signalling in adipose tissue from IL-6(-/-) mice.
Our findings question the role of IL-6 signalling in adipose tissue during exercise and suggest an indirect effect of this cytokine in the regulation of adipose tissue gene expression during exercise.
甘油酮生成是脂肪酸重新酯化的重要步骤，PEPCK 和 PDK4 被确定为该过程中的关键酶。我们之前已经表明，甘油酮生成酶，如 PDK4，在运动过程中会在白色脂肪组织中迅速诱导。最近的研究表明，IL-6 调节运动过程中脂肪组织的代谢和基因表达。有趣的是，有报道称 IL-6 可以直接降低 PEPCK 的表达。本研究的目的是确定 IL-6 在调节运动对小鼠脂肪组织甘油酮生成酶表达的影响中的作用。我们假设，与野生型对照相比，IL-6 缺乏小鼠脂肪组织中 PDK4 和 PEPCK 的运动介导诱导作用更大。
用 IL-6（150ng/ml）处理培养的附睾脂肪组织（eWAT）可增加 AMPK、ACC 和 STAT3 的磷酸化，并诱导 SOCS3 mRNA 水平，同时降低 PEPCK 和 PDK4 mRNA。AICAR 降低 PDK4 和 PEPCK 的表达。IL-6 对 AMPK 的激活不依赖于脂肪分解的增加。急性跑步机跑步（15 米/分钟，5%坡度，90 分钟）不会诱导 eWAT 中 SOCS3 的表达或增加 STAT3 的磷酸化，表明 IL-6 信号没有被激活。与运动后的 WT 小鼠相比，IL-6(-/-)小鼠 eWAT 中 PEPCK 和 PDK4 mRNA 表达的增加减弱，而 AMPK 磷酸化的相对增加更大。这些变化发生在 IL-6(-/-)小鼠脂肪组织中β-肾上腺素能信号的改变之外。
我们的发现对运动过程中脂肪组织中 IL-6 信号的作用提出了质疑，并表明这种细胞因子在运动过程中调节脂肪组织基因表达中的间接作用。
