Location: Immunity and Disease Prevention ResearchTitle: Endotoxin may not be the major cause of postprandial inflammation in adults who consume a single high-fat or moderately high-fat meal
|MO, ZHENZHEN - University Of California, Davis|
|BURNETT, DUSTIN - University Of California, Davis|
|RUTLEDGE, JOHN - University Of California, Davis|
Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/6/2020
Publication Date: N/A
Interpretive Summary: To determine the cause of postprandial (PP) inflammation, two cohorts of volunteers were given single meal with either 60% or 36% kcal from fat. Plasma endotoxin and free fatty acid concentrations in whole blood samples were determined in presence and absence of endotoxin inhibitor and lipoprotein lipase. Cytokine concentrations were also determined in the plasma and whole blood samples. Endotoxin in plasma was mostly below the assay sensitivity. Elevated plasma free fatty acid concentrations induced by lipoprotein lipase caused increased cytokine production in an LPS-independent manner in both studies. In conclusion, endotoxin may not be a major cause of PP inflammation in healthy subjects consuming typical American diets (34% fat), and plasma NEFA concentration may be an important determinant of PP inflammation.
Technical Abstract: 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 lipopolysaccharides (LPS) and LPS-mediated cytokine production in the postprandial blood (PPB). Methods: 98 volunteers (age: 37.3±1.5y) from the cross-sectional Phenotyping study (PS) and 62 volunteers (age: 26.8±1.2y) 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 24h at 37°C besides the Limulus Amebocytes lysate (LAL) assay. Repeated Measurements 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 (0.002EU/mL). PMB suppressed IL-1ß (P = 0.035) and IL-6 (P = 0.0487) productions in the 3h PPB of the PS after 24h 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 3h 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 free fatty acid (FFA) and cytokine (IL-1ß, IL-6, TNFa) 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.