BACKGROUND Our previous work demonstrated that a short-term high fat diet (HFD) increased fasting serum endotoxin, altered postprandial excursions of serum endotoxin, and led to metabolic and transcriptional responses in skeletal muscle in young, healthy male humans. PURPOSE The purpose of the present study was to determine if a short-term high fat diet: 1) increases intestinal permeability and, in turn, fasting endotoxin concentrations and 2) decreases postprandial skeletal muscle fat oxidation. METHODS Thirteen normal weight young adult males (BMI 23.1 ± 0.8 kg/m2, age 22.2 ± 0.4 years) were fed a control diet (55% carbohydrate, 30% fat, 9% of which was saturated, 15% protein) for two weeks, followed by 5 days of an isocaloric HFD (30% carbohydrate, 55% fat, 25% of which was saturated, 15% protein, isocaloric to the control diet). Intestinal permeability (via four sugar probe test) was assessed in the fasting state. Both before and after the HFD, a high fat meal challenge (HFM, 820 kcal, 25% carbohydrate, 63% fat, 26% of which was saturated, and 12% protein) was administered. After an overnight fast, blood samples were collected before and every hour for 4 h after the HFM to assess endotoxin, and other serum blood measures. Muscle biopsies were obtained from the vastus lateralis before and 4 h after the HFM in order to assess substrate oxidation (glucose, fatty acid and pyruvate) using radiolabeled techniques. Insulin sensitivity was assessed via intravenous glucose tolerance test. Intestinal permeability, blood samples and muscle biopsies were assessed in the same manner before and following the HFD. MAIN FINDINGS Intestinal permeability was not affected by HFD (p > 0.05), but fasting endotoxin increased two fold following the HFD (p = 0.04). Glucose oxidation and fatty acid oxidation in skeletal muscle homogenates significantly increased after the HFM before the HFD (+97%, and +106% respectively) but declined after the HFM following 5 days of the HFD (-24% and +16% respectively). Fatty acid suppressibility of pyruvate oxidation increased significantly after the HFM (+32%) but this physiological effect was abolished following 5 days of the HFD (+7%). Insulin sensitivity did not change following the HFD. CONCLUSION These findings demonstrate that in healthy young men, consuming an isocaloric HFD for 5 days increases fasting endotoxin, independent of changes in gut permeability. These changes in endotoxin are accompanied by a broad effect on skeletal muscle substrate metabolism including increases in postprandial fat oxidation. Importantly, the latter occurs independent of changes in body weight and whole-body insulin sensitivity.

中文翻译：

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人体短期食用高脂饮食后的血清内毒素，肠道通透性和骨骼肌代谢适应。

背景技术我们以前的工作表明，短期高脂饮食（HFD）可以增加年轻健康男性的空腹血清内毒素，改变血清内毒素的餐后偏移并导致骨骼肌的代谢和转录反应。目的本研究的目的是确定短期高脂饮食是否：1）增加肠通透性，进而禁食内毒素浓度，2）降低餐后骨骼肌脂肪氧化。方法对13名正常体重的成年男性（BMI 23.1±0.8 kg / m2，年龄22.2±0.4岁）进行了为期两周的对照饮食（55％的碳水化合物，30％的脂肪，9％的饱和脂肪，15％的蛋白质）。 ，然后进行5天的等热量HFD（30％碳水化合物，55％脂肪，其中25％饱和，15％蛋白质，相对于对照饮食是等热量的）。在禁食状态下评估肠通透性（通过四糖探针测试）。在HFD之前和之后，都进行了高脂膳食攻击（HFM，820 kcal，25％碳水化合物，63％脂肪，其中26％的脂肪饱和和12％的蛋白质）。禁食过夜后，在HFM之前和之后的4小时内每小时采集一次血液样本，以评估内毒素和其他血清血液指标。从HFM之前和之后的4 h从外侧股肌获得肌肉活检，以使用放射标记技术评估底物的氧化（葡萄糖，脂肪酸和丙酮酸）。通过静脉葡萄糖耐量试验评估胰岛素敏感性。在HFD之前和之后，以相同的方式评估肠通透性，血液样本和肌肉活检。主要发现肠通透性不受HFD影响（p> 0。05），但HFD后空腹内毒素增加了2倍（p = 0.04）。HFD前HFM后，骨骼肌匀浆中的葡萄糖氧化和脂肪酸氧化显着增加（分别为+ 97％和+ 106％），但在HFM后5天HFD后下降（分别为-24％和+ 16％） 。HFM后（+ 32％）丙酮酸氧化的脂肪酸抑制性显着提高（+ 32％），但HFD 5天（+ 7％）后，这种生理作用消失了。HFD后，胰岛素敏感性没有改变。结论这些发现表明，在健康的年轻男性中，服用等热量的HFD 5天会增加空腹内毒素，而与肠道通透性的变化无关。内毒素的这些变化伴随着对骨骼肌底物代谢的广泛影响，包括餐后脂肪氧化的增加。重要的是，后者的发生与体重和全身胰岛素敏感性的变化无关。