Postprandial Endotoxemia Linked With Chylomicrons and Lipopolysaccharides Handling in Obese Versus Lean Men: A Lipid Dose-Effect Trial

J Clin Endocrinol Metab. 2015 Sep;100(9):3427-35. doi: 10.1210/JC.2015-2518. Epub 2015 Jul 7.


Context: Postprandial endotoxemia is a metabolic risk factor, which has been shown to originate from the intestinal absorption of gut lipopolysaccharides (LPS) using nonphysiological high-fat tests.

Objective: This study aimed to determine whether different realistic fat amounts can modulate postprandial dynamics and handling of LPS by varying postprandial lipidemia in humans of different body mass indices.

Design, setting, and participants: In a randomized, controlled, cross-over study in nutrition research center, eight normal-weight (NW) and eight obese age-matched men, without diabetes nor dyslipidemia, ingested breakfasts containing 10 vs 40 g fat. Blood samples, leukocytes, and chylomicron-rich fractions were obtained during 8 h. Plasma and chylomicron-endotoxemia, plasma LPS transporters (LBP, sCD14) and IL-6, nuclear factor κB (NF-κB) translocation, and IL-6 gene expression of immune cells were measured.

Main outcome: The postprandial fatty acid handling after ingesting 40 g fat was previously published as primary outcome. The secondary outcomes were inflammatory ones including postprandial endotoxemia, LPS handling, and plasma markers of inflammation after ingesting 10 or 40 g fat.

Results: Chylomicronemia increased in all subjects according to ingested fat amount (P < .01), but only obese had higher postprandial endotoxemia after 40 g (P < .05). Obese subject chylomicrons were more enriched with LPS compared with NW (PBMI < .01). We observed neither NF-κB translocation, nor variation of IL-6 expression in leukocytes. In both groups, fat amount did not modify postprandial response of plasma IL-6. However, the area under the curve (AUC) of IL-6 in obese was higher than in NW (P < .05) parallel to higher fasting LPS-binding protein (LBP; P < .05). AUC of IL-6 was correlated with LBP (P < .01).

Conclusion: Postprandial endotoxemia is modulated by ingested fat amount in obese men. LPS handling in plasma through chylomicrons and LBP seems critical in driving the acute inflammatory response. The pathophysiological importance of repeated postprandial endotoxemia excursions and their contribution to a vicious cycle of LBP-driven low-grade inflammation deserve further investigation in the nutritional management of cardio-metabolic risk prevention.

Trial registration: NCT01249378.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Adult
  • Blood Glucose
  • Body Mass Index
  • Carrier Proteins / blood
  • Chylomicrons / blood*
  • Cross-Over Studies
  • Dietary Fats
  • Dose-Response Relationship, Drug
  • Endotoxemia / blood*
  • Humans
  • Insulin / blood
  • Lipopolysaccharides / blood*
  • Male
  • Membrane Glycoproteins / blood
  • Obesity / blood*
  • Postprandial Period / physiology*


  • Acute-Phase Proteins
  • Blood Glucose
  • Carrier Proteins
  • Chylomicrons
  • Dietary Fats
  • Insulin
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • lipopolysaccharide-binding protein

Associated data