Mo Zhenzhen, Huang Shurong, Burnett Dustin J, Rutledge John C, Hwang Daniel H
USDA-ARS Western Human Nutrition Research Center, 430 West Health Sciences Dr., Davis, CA 95616, USA.
Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA.
J Nutr. 2020 May 1;150(5):1303-1312. doi: 10.1093/jn/nxaa003.
Metabolic endotoxemia is considered a cause for high-fat diet (HFD)-induced inflammation. However, convincing experimental evidence in humans is scant.
We determined whether a HFD or moderately HFD increases LPS and LPS-mediated cytokine production in the postprandial blood (PPB).
Ninety-eight volunteers (age: 37.3 ± 1.5 y) from the cross-sectional phenotyping study (PS) and 62 volunteers (age: 26.8 ± 1.2 y) from the intervention study (IS) consumed a breakfast containing 60% kcal fat (HF) and 36% kcal fat (moderately HF), respectively. For the IS, only the results from the placebo group are presented. Blood samples were probed for LPS-mediated cytokine production by incubating them with LPS inhibitor polymyxin B (PMB) for 24 h at 37°C besides the Limulus amebocyte lysate (LAL) assay. Repeated-measures ANOVA was used to compare the temporal changes of metabolic profiles and treatment outcomes.
At least 87.5% of the plasma LPS measurements in 32 PS volunteers from each time point were below the LAL assay sensitivity (0.002 EU/mL). PMB suppressed IL-1β (P = 0.035) and IL-6 (P = 0.0487) production in the 3 h PPB of the PS after 24 h incubation at 37°C compared to the vehicle control, suggesting the presence of LPS. However, the amount of LPS did not increase the cytokine concentrations in the 3 h PPB above the fasting concentrations. Such suppression was not detected in the PPB of the IS. Treating whole blood with lipoprotein lipase (LPL) significantly (P < 0.05) increased FFA and cytokine (IL-1β, IL-6, TNF-α) concentrations in both studies.
LPS may not be the major cause of postprandial inflammation in healthy adults consuming a moderately HF meal (36% kcal fat, similar to the typical American diet) or a HF meal (60% kcal fat). Plasma FFAs may modulate postprandial inflammation. The prevailing concept of HFD-induced metabolic endotoxemia requires careful re-evaluation. The PS was registered at clinicaltrials.gov as NCT02367287 and the IS as NCT02472171.
代谢性内毒素血症被认为是高脂饮食（HFD）诱导炎症的一个原因。然而，在人类中令人信服的实验证据很少。
我们确定HFD或适度HFD是否会增加餐后血液（PPB）中脂多糖（LPS）和LPS介导的细胞因子产生。
来自横断面表型研究（PS）的98名志愿者（年龄：37.3±1.5岁）和来自干预研究（IS）的62名志愿者（年龄：26.8±1.2岁）分别食用了含60%千卡脂肪（HF）和36%千卡脂肪（适度HF）的早餐。对于IS，仅呈现安慰剂组的结果。除了鲎试剂（LAL）检测外，将血样与LPS抑制剂多粘菌素B（PMB）在37°C孵育24小时，以检测LPS介导的细胞因子产生。采用重复测量方差分析来比较代谢谱和治疗结果的时间变化。
来自PS的32名志愿者在每个时间点至少87.5%的血浆LPS测量值低于LAL检测灵敏度（0.002 EU/mL）。与载体对照相比，在37°C孵育24小时后，PMB在PS的3小时PPB中抑制了IL-1β（P = 0.035）和IL-6（P = 0.0487）的产生，表明存在LPS。然而，LPS的量并未使3小时PPB中的细胞因子浓度高于空腹浓度。在IS的PPB中未检测到这种抑制作用。在两项研究中，用脂蛋白脂肪酶（LPL）处理全血均显著（P < 0.05）增加了游离脂肪酸（FFA）和细胞因子（IL-1β、IL-6、TNF-α）的浓度。
对于食用适度HF餐（36%千卡脂肪，类似于典型美国饮食）或HF餐（60%千卡脂肪）的健康成年人，LPS可能不是餐后炎症的主要原因。血浆FFA可能调节餐后炎症。HFD诱导的代谢性内毒素血症这一普遍概念需要仔细重新评估。PS在clinicaltrials.gov上注册为NCT02367287，IS注册为NCT02472171。
