Mechanisms of fructose-induced hypertriglyceridaemia in the rat. Activation of hepatic pyruvate dehydrogenase through inhibition of pyruvate dehydrogenase kinase.
Mechanisms of fructose-induced hypertriglyceridaemia in the rat. Activation of hepatic pyruvate dehydrogenase through inhibition of pyruvate dehydrogenase kinase.
复制标题
果糖诱导大鼠高甘油三酯血症的机制。
DOI：
10.1042/bj2820753
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Hellerstein,MK
中科院分区：
文献类型：
--
作者：
Park,OJ;Cesar,D;Faix,D;Wu,K;Shackleton,CH;Hellerstein,MK
1. 测定含70%葡萄糖或70%果糖的纯化饲料对大鼠肝丙酮酸脱氢酶（PDHa）激活状态、线粒体PDH激酶活性、血浆三酰甘油（TG）和肝脏脂肪生成的影响。 2. 尽管每日食物摄入量较少，但在饮食 3-5 周后，与葡萄糖喂养组相比，果糖喂养组的血浆 TG 显着增加（125 +/- 45 mg/dl 对比 57 +/- 19 mg/dl；P 小于 0.002）。 3. 果糖喂养大鼠的肝脏 PDHa 是葡萄糖喂养大鼠的 144%（15.4 +/- 1.2% 对比 10.7 +/- 0.5%；P 小于 0.002），而心肌 PDHa 没有差异（45.5 +/- 6.6% 对比 41.0 +/- 7.8%）。 4. 饲喂果糖后，内在肝 PDH 激酶活性降低至葡萄糖饲喂值的 34%（-k = 3.56 +/- 0.39 对比 10.41 +/- 1.85 min-1；P 小于 0.005）。 5. 通过稳定同位素质谱法测量，果糖喂养的大鼠中肝脏脂肪生成对极低密度脂蛋白棕榈酸酯的贡献分数为 10.49 +/- 2.42% (n = 8)，而葡萄糖喂养的大鼠中为 5.55 +/- 1.38% (n = 9)（P 小于 0.05），并且食物喂养的大鼠为 2.66 +/- 2.39% (n = 3)（与果糖喂养组相比，P 小于 0.05）。果糖喂养组中脂肪从头生成对循环 TG 的绝对贡献也显着高于葡萄糖喂养组（14.9 +/- 5.1 mg/dl 对比 2.9 +/- 0.6 mg/dl；P 小于 0.05）6. 果糖喂养组大鼠的门静脉胰岛素浓度显着更高（206 +/- 49 mu 单位/ml 对比 81 +/- 49 mu 单位/ml） 15μ单位/ml；P小于0.05)。 7. 总之，膳食果糖似乎对肝 PDH 具有特异性激活作用，至少部分是通过抑制 PDH 激酶介导的。这些结果与通过肝 PDH 的流量增加和新脂肪的合成一致，而不仅仅是非酯化脂肪酸的再酯化增加。
1. The effects of purified diets containing 70% glucose or 70% fructose on the activation state of hepatic pyruvate dehydrogenase (PDHa), activity of mitochondrial PDH kinase, plasma triacylglycerols (TG) and hepatic lipogenesis de novo in rats were measured. 2. Plasma TG were significantly increased in the fructose-fed compared with the glucose-fed group (125 +/- 45 mg/dl versus 57 +/- 19 mg/dl; P less than 0.002) after 3-5 weeks on the diet despite less daily food intake. 3. Hepatic PDHa in fructose-fed rats was 144% of the value in glucose-fed rats (15.4 +/- 1.2% versus 10.7 +/- 0.5%; P less than 0.002), whereas cardiac muscle PDHa was not different (45.5 +/- 6.6% versus 41.0 +/- 7.8%). 4. Intrinsic hepatic PDH kinase activity was decreased to 34% of glucose-fed values by fructose feeding (-k = 3.56 +/- 0.39 versus 10.41 +/- 1.85 min-1; P less than 0.005). 5. The fractional contribution to very-low-density-lipoprotein palmitate from hepatic lipogenesis de novo, measured by a stable-isotope mass-spectrometric method, was 10.49 +/- 2.42% (n = 8) in fructose-fed rats versus 5.55 +/- 1.38% (n = 9) in glucose-fed rats (P less than 0.05), and 2.66 +/- 2.39% (n = 3) in chow-fed rats (P less than 0.05 versus fructose-fed group). The absolute contribution to circulating TG from lipogenesis de novo was also significantly higher in the fructose-fed than in the glucose-fed group (14.9 +/- 5.1 mg/dl versus 2.9 +/- 0.6 mg/dl; P less than 0.05) 6. Portal insulin concentrations were significantly higher in the fructose-fed rats (206 +/- 49 mu-units/ml versus 81 +/- 15 mu-units/ml; P less than 0.05). 7. In conclusion, dietary fructose appears to have a specific activating effect on hepatic PDH, mediated at least in part by inhibition of PDH kinase. These results are consistent with increased flux through hepatic PDH and synthesis of new fat, not just increased re-esterification of non-esterified fatty acids.