Obesity and metabolic syndrome are strongly associated with cancer, and these disorders may share a common mechanism. Recently, fructose has emerged as a driving force to develop obesity and metabolic syndrome. Thus, we assume that fructose may be the mechanism to explain why obesity and metabolic syndrome are linked with cancer. Clinical and experimental evidence showed that fructose intake was associated with cancer growth and that fructose transporters are upregulated in various malignant tumors. Interestingly, fructose metabolism can be driven under low oxygen conditions, accelerates glucose utilization, and exhibits distinct effects as compared to glucose, including production of uric acid and lactate as major byproducts. Fructose promotes the Warburg effect to preferentially downregulate mitochondrial respiration and increases aerobic glycolysis that may aid metastases that initially have low oxygen supply. In the process, uric acid may facilitate carcinogenesis by inhibiting the TCA cycle, stimulating cell proliferation by mitochondrial ROS, and blocking fatty acid oxidation. Lactate may also contribute to cancer growth by suppressing fat oxidation and inducing oncogene expression. The ability of fructose metabolism to directly stimulate the glycolytic pathway may have been protective for animals living with limited access to oxygen, but may be deleterious toward stimulating cancer growth and metastasis for humans in modern society. Blocking fructose metabolism may be a novel approach for the prevention and treatment of cancer.

中文翻译：

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果糖有助于癌症生长的瓦尔堡效应


肥胖和代谢综合征与癌症密切相关，这些疾病可能具有共同的机制。最近，果糖已成为肥胖和代谢综合征的驱动力。因此，我们假设果糖可能是解释肥胖和代谢综合征与癌症相关的机制。临床和实验证据表明，果糖摄入量与癌症生长相关，并且果糖转运蛋白在各种恶性肿瘤中上调。有趣的是，果糖代谢可以在低氧条件下驱动，加速葡萄糖利用，并且与葡萄糖相比表现出独特的效果，包括产生尿酸和乳酸作为主要副产物。果糖促进瓦伯格效应，优先下调线粒体呼吸并增加有氧糖酵解，这可能有助于最初氧供应不足的转移。在此过程中，尿酸可能通过抑制 TCA 循环、通过线粒体 ROS 刺激细胞增殖以及阻止脂肪酸氧化来促进癌变。乳酸还可能通过抑制脂肪氧化和诱导癌基因表达来促进癌症生长。果糖代谢直接刺激糖酵解途径的能力可能对氧气有限的动物具有保护作用，但可能对刺激现代社会人类的癌症生长和转移有害。阻断果糖代谢可能是预防和治疗癌症的新方法。