Department of Human Nutrition, Foods and Exercise, Virginia Tech, 338 Wallace Hall, 295 West Campus Drive, Blacksburg, VA 24061, USA.
Department of Human Nutrition, Foods and Exercise, Virginia Tech, 338 Wallace Hall, 295 West Campus Drive, Blacksburg, VA 24061, USA; Virginia Tech Metabolic Phenotyping Core Facility, Integrated Life Science Building, 1981 Kraft Drive, Blacksburg, VA 24060, USA.
Metabolism. 2020 Feb;103:154041. doi: 10.1016/j.metabol.2019.154041. Epub 2019 Nov 28.
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.
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.
Thirteen normal weight young adult males (BMI 23.1 ± 0.8 kg/m, 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.
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.
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.
我们之前的工作表明，短期高脂肪饮食（HFD）会增加空腹血清内毒素，改变餐后血清内毒素的波动，并导致年轻健康男性的骨骼肌发生代谢和转录反应。
本研究旨在确定短期高脂肪饮食是否会：1）增加肠道通透性，进而增加空腹内毒素浓度，2）降低餐后骨骼肌脂肪氧化。
13 名正常体重的年轻成年男性（BMI 23.1±0.8kg/m，年龄 22.2±0.4 岁）连续两周食用对照饮食（55%碳水化合物，30%脂肪，其中 9%为饱和脂肪，15%蛋白质），然后再食用 5 天等热量的高脂肪饮食（30%碳水化合物，55%脂肪，其中 25%为饱和脂肪，15%蛋白质，与对照饮食等热量）。在空腹状态下通过四种糖探针测试评估肠道通透性。在 HFD 前后，给予高脂肪餐挑战（HFM，820kcal，25%碳水化合物，63%脂肪，其中 26%为饱和脂肪，12%蛋白质）。禁食一夜后，在 HFM 前和 HFM 后 4 小时内每小时采集血样，以评估内毒素和其他血清指标。在 HFM 前后 4 小时从股外侧肌获取肌肉活检，以使用放射性标记技术评估底物氧化（葡萄糖、脂肪酸和丙酮酸）。通过静脉内葡萄糖耐量试验评估胰岛素敏感性。在 HFD 前后以相同的方式评估肠道通透性、血样和肌肉活检。
HFD 并未影响肠道通透性（p＞0.05），但 HFD 后空腹内毒素增加了两倍（p=0.04）。在 HFM 后，HFD 前骨骼肌匀浆中的葡萄糖氧化和脂肪酸氧化分别显著增加（分别增加 97%和 106%），但在 HFD 后 5 天内，HFM 后减少（分别减少 24%和 16%）。HFM 后，丙酮酸氧化的脂肪酸抑制作用显著增加（增加 32%），但在 HFD 后 5 天内这种生理效应消失（增加 7%）。HFD 后胰岛素敏感性没有变化。
这些发现表明，在健康的年轻男性中，连续 5 天摄入等热量的高脂肪饮食会增加空腹内毒素，而不改变肠道通透性。这些内毒素的变化伴随着骨骼肌底物代谢的广泛变化，包括餐后脂肪氧化增加。重要的是，后一种变化发生在体重和全身胰岛素敏感性没有变化的情况下。
