Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients

Abstract

Obesity is an increasingly prevalent health problem, very often accompanied by other diseases, the most common being insulin resistance, type 2 diabetes mellitus, and cardiovascular complications ( 1, 2 ). Furthermore, an association has been reported between obesity and both oxidative stress and increased infl ammation ( 3, 4 ). Obesity facilitates the development of a low-grade infl ammatory state, characterized by increased plasma levels of proinfl ammatory cytokines ( 4 ). However, the factors that trigger this low-grade infl ammation in obesity are unclear. Postprandial lipidemia has recently emerged as a potential candidate because the ingestion of a highfat meal leads to the systemic increase of a wide range of infl ammatory mediators ( 5-7 ) and an increase in oxidative stress markers ( 8 ). However, the cause of these postprandial events that occur in association with the postprandial triglyceride response remains poorly understood. A possible link is bacterial endotoxin [lipopolysaccharide (LPS)], a component of the Gram-negative bacteria cell wall that is present in large quantities in the human gut ( 9 ). Endotoxins circulate in the plasma Abstract The low-grade infl ammation observed in obesity has been associated with a high-fat diet, though this relation is not fully understood. Bacterial endotoxin, produced by gut microbiota, may be the linking factor. However, this has not been confi rmed in obese patients. To study the relationship between a high-fat diet and bacterial endotoxin, we analyzed postprandial endotoxemia in morbidly obese patients after a fat overload. The endotoxin levels were determined in serum and the chylomicron fraction at baseline and 3 h after a fat overload in 40 morbidly obese patients and their levels related with the degree of insulin resistance and postprandial hypertriglyceridemia. The morbidly obese patients with the highest postprandial hypertriglyceridemia showed a signifi cant increase in lipopolysaccharide (LPS) levels in serum and the chylomicron fraction after the fat overload. Postprandial chylomicron LPS levels correlated positively with the di ff erence between postprandial triglycerides and baseline triglycerides. There were no signifi cant correlations between C-reactive protein (CRP) and LPS levels. The main variables contributing to serum LPS levels after fat overload were baseline and postprandial triglyceride levels but not glucose or insulin resistance. Additionally, superoxide dismutase activity decreased signifi cantly after the fat overload. Postprandial LPS increase after a fat overload is related to postprandial hypertriglyceridemia but not to degree of insulin resistance in morbidly obese patients. -Clemente-Postigo, M., M. I. Queipo-Ortuño,

Dietary lipid emulsions and endotoxemia

“…Mixed hyperlipidic/hyperglucidic meals (51 g lipids, 81 g carbohydrates) also increase plasma LPS in the postprandial phase in healthy lean men (Ghanim et al, 2009. Recent studies confirm these results of postprandial endotoxemia in type 2 diabetic subjects consuming 75 g of lipids (Harte et al, 2012) and in morbidly obese subjects consuming a 50 g lipid load (Clemente-Postigo et al, 2012). Among postprandial studies, some used dairy fat (butter or cream), other used mixed fatrich foods (often eggs and sausage) or simple oil load or, in the form of single food or into mixed meals, and altogether fat intake was high (Tab.…”

Higher plasma lipopolysaccharide concentrations are associated with less favorable phenotype in overweight/obese men

“…In the present study, these indices were similar between subjects with slightly different phenotypes, especially regarding the insulin resistance markers. Contradictory results regarding the association of these indices with LPS concentration have been reported previously [21,37]. We showed that sagittal abdominal diameter, an unusual indicator of abdominal obesity, distinguished subjects with different concentrations of plasma LPS.…”

Endotoxemia Analysis by the Limulus Amoebocyte Lysate Assay in Different Mammal Species Used in Metabolic Studies

“…In another study mice plasma were not diluted, endotoxemia was around 0.8 EU/mL (Lonza endpoint kit) but no information on the preparation was provided [28]. The same is observed in humans: only some authors described their procedure to prepare sample, and a study led by Clemente-Postigo et al [29] did not dilute human plasma with a Lonza kit contrary to Erridge et al [30] which diluted the samples at 1/10 (as us) with a Cambrex kit. However in these 2 studies endotoxemia values were around 0.8 EU/mL like in our experiments using a Cape Cod kit.…”