Endotoxin May Not Be the Major Cause of Postprandial Inflammation in Adults Who Consume a Single High-Fat or Moderately High-Fat Meal

Zhenzhen Mo, Shurong Huang, Dustin J. Burnett, John C. Rutledge, Daniel H. Hwang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


BACKGROUND: Metabolic endotoxemia is considered a cause for high-fat diet (HFD)-induced inflammation. However, convincing experimental evidence in humans is scant. OBJECTIVE: We determined whether a HFD or moderately HFD increases LPS and LPS-mediated cytokine production in the postprandial blood (PPB). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)1303-1312
Number of pages10
JournalThe Journal of nutrition
Issue number5
StatePublished - May 1 2020


  • clinical trials
  • diet and dietary lipids
  • diet effects/lipid metabolism
  • high-fat diet
  • inflammation
  • lipase/lipoprotein
  • macrophages/monocytes
  • plasma cytokines
  • postprandial metabolic endotoxemia
  • toll-like receptor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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