Postprandial Endotoxin Transporters LBP and sCD14 Differ in Obese vs. Overweight and Normal Weight Men during Fat-Rich Meal Digestion

Abstract

Circulating levels of lipopolysaccharide-binding protein (LBP) and soluble cluster of differentiation 14 (sCD14) are recognized as clinical markers of endotoxemia. In obese men, postprandial endotoxemia is modulated by the amount of fat ingested, being higher compared to normal-weight (NW) subjects. Relative variations of LBP/sCD14 ratio in response to overfeeding are also considered important in the inflammation set-up, as measured through IL-6 concentration. We tested the hypothesis that postprandial LBP and sCD14 circulating concentrations differed in obese vs. overweight and NW men after a fat-rich meal. We thus analyzed the postprandial kinetics of LBP and sCD14 in the context of two clinical trials involving postprandial tests in normal-, over-weight and obese men. In the first clinical trial eight NW and 8 obese men ingested breakfasts containing 10 vs. 40 g of fat. In the second clinical trial, 18 healthy men were overfed during 8 weeks. sCD14, LBP and Il-6 were measured in all subjects during 5 h after test meal. Obese men presented a higher fasting and postprandial LBP concentration in plasma than NW men regardless of fat load, while postprandial sCD14 was similar in both groups. Irrespective of the overfeeding treatment, we observed postprandial increase of sCD14 and decrease of LBP before and after OF. In obese individuals receiving a 10 g fat load, whereas IL-6 increased 5h after meal, LBP and sCD14 did not increase. No direct association between the postprandial kinetics of endotoxemia markers sCD14 and LBP and of inflammation in obese men was observed in this study.

Postprandial lipid and vascular responses following consumption of a commercially-relevant interesterified palmitic acid-rich spread in comparison to functionally-equivalent non-interesterified spread and spreadable butter: a randomised controlled trial in healthy adults

“…65,66 We found no significant postprandial increases in endotoxemia markers following spreads, but there was an elevation in sCD14 at 8 h following RO. Although this was not statistically significant using Bonferroni-adjusted pairwise comparisons, the trend is consistent with previous findings suggesting that high-fat meals enhanced transient postprandial endotoxemia, 30,32,63,67 including a postprandial rise of sCD14. 30,32 Further, these results agree with a study showing that 8-week rapeseed oil feeding in mice induced elevated levels of sCD14, but not increased inflammation measured by IL-6 in contrast to the response to a palm oil diet.…”

“…Although this was not statistically significant using Bonferroni-adjusted pairwise comparisons, the trend is consistent with previous findings suggesting that high-fat meals enhanced transient postprandial endotoxemia, 30,32,63,67 including a postprandial rise of sCD14. 30,32 Further, these results agree with a study showing that 8-week rapeseed oil feeding in mice induced elevated levels of sCD14, but not increased inflammation measured by IL-6 in contrast to the response to a palm oil diet. 68 We found that inflammation increased after all high-fat meals, but the IL-6 did not differ between fat types.…”

“…Lipopolysaccharide (LPS)-binding protein (LBP, an LPS transporter) and soluble cluster of differentiation 14 (sCD14, a glycoprotein expressed on the surface of monocytes and macrophages and a soluble receptor that receives LPS from LBP, resulting in endothelial cell activation), and the ratio between them, are used as more stable markers of endotoxin exposure than direct measurement of LPS, 29 and have been shown previously to be modified postprandially following high fat meals. 30,31 Plasma LBP and sCD14 concentrations were assayed using ELISA kits (CliniSciences and R&D Systems; Nanterre, France) as described elsewhere. 32…”

The Gut-Liver Axis in Cholestatic Liver Diseases

“…LPS-binding protein (LBP) correlates with LPS and binds to receptor CD14, existing in soluble (sCD14) and in membrane-bound (mCD14) forms, which is involved in triggering inflammation. LBP and sCD14 can be measured with sandwich ELISA kits in plasma and are useful surrogate parameters for endotoxemia [10,85,86]. Calprotectin, a protein located mainly in neutrophils, but also in macrophages and monocytes, is secreted into the intestinal lumen during ongoing inflammation of the intestine and can be measured in feces as a marker of intestinal inflammation [87].…”

Increased plasma lipopolysaccharide-binding protein and altered inflammatory mediators in overweight women suggest a state of subclinical endotoxemia

“…Until longitudinal data concerning subclinical endotoxemia are available, it may be prudent to institute proactive measures to monitor and reduce the circulating levels of LBP, as a surrogate biomarker for endotoxemia. As composition of the diet has been shown to be a critical driver of metabolic endotoxemia (reviewed in (57)), with high saturated fat ingestion causing postprandial endotoxemia with increases in IL-6 even in lean subjects (58, 59), dietary intervention would be a reasonable initial step. Other possibilities include pharmacological interventions, including the potential development of anti-LPS peptides which neutralize LPS signaling of immune system activation (57).…”