Low-grade inflammation is now recognized as a hallmark of obesity pathophysiology. Recent interest has focused on the role of endotoxins absorbed during high fat meals. LBP and sCD14 have also been suggested as clinical markers of endotoxemia and in mice, the ratio LBP/sCD14 has been associated with high-fat diet induced inflammation. We tested the hypothesis that healthy subjects develop inflammation differently during overfeeding-induced weight gain according to the changes of LBP/sCD14 ratio in plasma.

Eighteen lean to overweight subjects were submitted to overfeeding (OF) during 8 weeks (+ 760kcal/day). Endotoxemia, sCD14, LBP and IL-6 were measured before and after OF at fasting (n=18), and in the postprandial phase after an 882-kcal test meal in a subcohort (n=8).

In the cohort, no effect of OF was observed on fasting IL-6 but OF induced an increase of LBP/sCD14 ratio (P=0,017). Subjects were divided into tertiles regarding their variation of LBP/sCD14 ratio due to OF. Subjects in the highest tertile (+ 90 % of LBP/sCD14 ratio) increased plasma IL-6 (+ 26%) compared with the lowest tertile (no increase of LBP/sCD14 ratio ; − 31 % of plasma IL-6 ; P<0,05). This was due to a decrease of plasma sCD14 (P<0,05), while in the middle tertile the increased ratio (+ 30 %) was due to increased LBP (P<0,05). OF induced an increased postprandial accumulation of endotoxins regardless of tertile (P<0,05). However, OF increased the fasting and postprandial IL-6 concentrations only in subjects of the middle and highest tertiles (P<0,01 vs baseline and vs lowest tertile).

Overfeeding increases postprandial endotoxemia but the inflammatory outcome appears to be modulated by the handling of endotoxins by different transporters in plasma. This study supports a new concept whereby the setup of low-grade inflammation during the initial phase of weight gain is linked to the relative variations of LBP and sCD14.