Center for Neurosciences and Cell Biology, University of Coimbra, UC-Biotech, Biocant Park, 3060-197, Cantanhede, Portugal.
Sci Rep. 2020 Jul 30;10(1):12852. doi: 10.1038/s41598-020-69820-3.
Excessive sugar intake including high-fructose corn syrup (HFCS) is implicated in the rise of obesity, insulin resistance and non-alcoholic fatty liver disease. Liver glycogen synthesis is influenced by both fructose and insulin signaling. Therefore, the effect of HFCS on hepatic glycogenesis was evaluated in mice feeding ad-libitum. Using deuterated water: the fraction of glycogen derived from triose-P sources, Krebs cycle substrates, and direct pathway + cycling, was measured in 9 normal-chow fed mice (NC) and 12 mice fed normal chow plus a 55% fructose/45% glucose mix in the drinking water at 30% w/v (HFCS-55). This was enriched with [U-C]fructose or [U-C]glucose to determine the contribution of each to glycogenesis. For NC, direct pathway + cycling, Krebs cycle, and triose-P sources accounted for 66 ± 0.7%, 23 ± 0.8% and 11 ± 0.4% of glycogen synthesis, respectively. HFCS-55 mice had similar direct pathway + cycling (64 ± 1%) but lower Krebs cycle (12 ± 1%, p < 0.001) and higher triose-P contributions (24 ± 1%, p < 0.001). HFCS-55-fructose contributed 17 ± 1% via triose-P and 2 ± 0% via Krebs cycle. HFCS-55-glucose contributed 16 ± 3% via direct pathway and 1 ± 0% via Krebs cycle. In conclusion, HFCS-55 supplementation resulted in similar hepatic glycogen deposition rates. Indirect pathway contributions shifted from Krebs cycle to Triose-P sources reflecting HFCS-55-fructose utilization, while HFCS-55-glucose was incorporated almost exclusively by the direct pathway.
过量的糖摄入，包括高果糖玉米糖浆（HFCS），与肥胖、胰岛素抵抗和非酒精性脂肪肝病的上升有关。肝脏糖原合成受果糖和胰岛素信号的影响。因此，我们评估了 HFCS 对自由进食的小鼠肝糖生成的影响。使用氘水：三碳糖-P 来源、柠檬酸循环底物和直接途径+循环衍生的糖原分数，在 9 只正常喂养的小鼠（NC）和 12 只在饮用水中添加 30%w/v（HFCS-55）的正常饲料加 55%果糖/45%葡萄糖混合物的小鼠中进行了测量。用[U-C]果糖或[U-C]葡萄糖对其进行了富集，以确定每种物质对糖生成的贡献。对于 NC，直接途径+循环、柠檬酸循环和三碳糖-P 来源分别占糖原合成的 66±0.7%、23±0.8%和 11±0.4%。HFCS-55 小鼠的直接途径+循环相似（64±1%），但柠檬酸循环较低（12±1%，p<0.001），三碳糖-P 贡献较高（24±1%，p<0.001）。HFCS-55-果糖通过三碳糖贡献 17±1%，通过柠檬酸循环贡献 2±0%。HFCS-55-葡萄糖通过直接途径贡献 16±3%，通过柠檬酸循环贡献 1±0%。总之，HFCS-55 的补充导致肝糖原沉积率相似。间接途径的贡献从柠檬酸循环转移到三碳糖-P 来源，反映了 HFCS-55-果糖的利用，而 HFCS-55-葡萄糖几乎完全通过直接途径被纳入。
