Tsameret Shani, Chapnik Nava, Froy Oren
Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Metabolites. 2023 Jan 17;13(2):138. doi: 10.3390/metabo13020138.
We aimed to explore whether fructose in the absence or presence of fatty acids modulates circadian metabolism in AML-12 hepatocytes. Fructose treatment under steatosis conditions (FruFA) led to fat synthesis resulting in increased triglycerides and cholesterol content. Fructose led to reduced activity of the AMPK and mTOR-signaling pathway. However, FruFA treatment led to inhibition of the AMPK signaling pathway but activation of the mTOR pathway. Fructose also increased the expression of inflammatory markers, whereas the addition of fatty acids dampened their circadian expression. At the clock level, fructose or FruFA altered the expression of the core clock. More specifically, fructose led to altered expression of the BMAL1-RORα-REV-ERBα axis, together with reduced phosphorylated BMAL1 levels. In conclusion, our results show that hepatocytes treated with fructose respond differently if fatty acids are present, leading to a differential effect on metabolism and circadian rhythms. This is achieved by modulating BMAL1 activity and expression.
我们旨在探究在不存在或存在脂肪酸的情况下，果糖是否会调节AML-12肝细胞中的昼夜节律代谢。在脂肪变性条件下进行果糖处理（FruFA）会导致脂肪合成，从而使甘油三酯和胆固醇含量增加。果糖会导致AMPK和mTOR信号通路的活性降低。然而，FruFA处理会导致AMPK信号通路受到抑制，但mTOR通路被激活。果糖还会增加炎症标志物的表达，而添加脂肪酸则会减弱它们的昼夜节律表达。在生物钟水平上，果糖或FruFA会改变核心生物钟的表达。更具体地说，果糖会导致BMAL1-RORα-REV-ERBα轴的表达发生改变，同时磷酸化的BMAL1水平降低。总之，我们的结果表明，如果存在脂肪酸，用果糖处理的肝细胞会有不同的反应，从而对代谢和昼夜节律产生不同的影响。这是通过调节BMAL1的活性和表达来实现的。
