Chapnik Nava, Rozenblit-Susan Sigal, Genzer Yoni, Froy Oren
Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Int J Biochem Cell Biol. 2016 Aug;77(Pt A):35-40. doi: 10.1016/j.biocel.2016.05.019. Epub 2016 May 27.
In the liver, fructose bypasses the main rate-limiting step of glycolysis at the level of phosphofructokinase, allowing it to act as an unregulated substrate for de novo lipogenesis. It has been reported that consumption of large amounts of fructose increases de novo lipogenesis in the liver. However, the effect of fructose on ectopic deposition of muscle fat has been under dispute. Our aim was to study the effect of fructose on levels of genes and proteins involved in fatty acid oxidation and synthesis in hepatocytes vs. muscle cells. In addition, as fat accumulation leads to disruption of daily rhythms, we tested the effect of fructose treatment on clock gene expression. AML-12 hepatocytes and C2C12 myotubes were treated with fructose or glucose for 2 consecutive 24-h cycles and harvested every 6h. In contrast to glucose, fructose disrupted clock gene rhythms in hepatocytes, but in myotubes, it led to more robust rhythms. Fructose led to low levels of phosphorylated AMP-activated protein kinase (pAMPK) and high levels of LIPIN1 in hepatocytes compared with glucose. In contrast, fructose led to high pAMPK and low LIPIN1 and microsomal triacylglycerol transfer protein (MTTP) levels in myotubes compared with glucose. Analysis of fat content revealed that fructose led to less fat accumulation in myotubes compared to hepatocytes. In summary, fructose shifts metabolism towards fatty acid synthesis and clock disruption in hepatocytes, but not in myotubes.
在肝脏中，果糖绕过了糖酵解在磷酸果糖激酶水平的主要限速步骤，使其能够作为从头脂肪生成的不受调控的底物。据报道，大量摄入果糖会增加肝脏中的从头脂肪生成。然而，果糖对肌肉脂肪异位沉积的影响一直存在争议。我们的目的是研究果糖对肝细胞与肌肉细胞中参与脂肪酸氧化和合成的基因和蛋白质水平的影响。此外，由于脂肪积累会导致日常节律紊乱，我们测试了果糖处理对时钟基因表达的影响。将AML-12肝细胞和C2C12肌管分别用果糖或葡萄糖处理，连续进行2个24小时周期，每6小时收获一次。与葡萄糖相比，果糖扰乱了肝细胞中的时钟基因节律，但在肌管中，它导致了更强健的节律。与葡萄糖相比，果糖使肝细胞中磷酸化的AMP激活蛋白激酶（pAMPK）水平降低，LIPIN1水平升高。相反，与葡萄糖相比，果糖使肌管中的pAMPK水平升高，LIPIN1和微粒体三酰甘油转移蛋白（MTTP）水平降低。脂肪含量分析显示，与肝细胞相比，果糖导致肌管中的脂肪积累减少。总之，果糖使肝细胞的代谢向脂肪酸合成和时钟紊乱转变，但在肌管中并非如此。
