Determinants of Serum Concentrations of Lipopolysaccharide-Binding Protein (LBP) in the Adult Population: The Role of Obesity

Abstract

Background and AimAssessment of serum concentration of lipopolysaccharide (LPS)-binding protein (LBP) has been suggested as a useful biomarker to indicate activation of innate immune responses to microbial products. We investigated LBP concentrations and associations with demographics, lifestyle factors, and common metabolic abnormalities in adults. We also examined if LBP concentrations were associated with common polymorphisms in genes coding for LBP (rs2232618), CD14 (rs2569190), and TLR4 (rs4986790), the molecules responsible for the innate immune response to LPS, or serum levels of soluble CD14 (sCD14) and proinflammatory cytokines.MethodsSerum LBP was measured with a commercial immunoassay in a random sample of the adult population (n = 420, 45% males, age 18–92 years) from a single municipality.ResultsSerum LBP concentrations increased with age (P<0.001) and were higher in individuals who were overweight or obese than in normal-weight individuals (P<0.001). Similarly, LBP concentrations were higher in individuals with metabolic syndrome than in individuals without it (P<0.001). Among metabolic syndrome components, LBP concentrations were independently associated with abdominal obesity (P = 0.002) and low concentrations of HDL-cholesterol (P<0.001). Serum LBP concentrations tended to be independently associated with smoking (P = 0.05), but not with alcohol consumption. Likewise, there was not significant association between LBP concentrations and gene polymorphisms. Concentrations of LBP significantly correlated with serum levels of proinflammatory cytokines (IL-6 and IL-8), sCD14, and with liver enzymes.ConclusionsSerum LBP concentrations increased with age. Overweight, obesity, and having metabolic syndrome (particularly, low HDL cholesterol levels) were associated with higher LBP concentrations. These findings are consistent with microbial exposure playing a role in these inflammatory, metabolic abnormalities.

A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation- and obesity-associated adipose tissue dysfunction

“…LBP recognises the lipid A component of LPS monomers and accelerates LPS binding to CD14, enhancing the sensitivity of cells to LPS [12,13]. Previous reports have shown a strong association between concentration of circulating LBP and obesity-associated metabolic disturbances [14][15][16][17]. In agreement with these studies, we found that concentrations of circulating LBP increased in obesity and decreased after weight loss [18].…”

“…In agreement with these studies, we found that concentrations of circulating LBP increased in obesity and decreased after weight loss [18]. However, despite the association of LBP concentration with changes in fat mass, all these studies claimed the liver as the main source of variation in the concentration of circulating LBP [14][15][16][17][18]. A recent study described LBP secretion by 3T3-L1 adipocytes [19] and increased serum LBP levels in genetically and diet-induced obese mice after LPS injection, but AT LBP production was not investigated [19].…”

“…A dramatic upregulation of circulating LBP concentration has been reported in obese individuals with increased fat mass [16][17][18]. Although circulating LBP is thought to derive from the liver [13,32], the close relationship between circulating LBP and obesity led us to investigate the possible contribution of AT to circulating LBP levels.…”

L’altération de la perméabilité intestinale : chaînon manquant entre dysbiose et inflammation au cours de l’obésité ?

“…Chez l'homme, en situation de sepsis, une corrélation a été montrée entre les taux sériques de LPS et de LBP (LPS-binding protein) plasmatique, une protéine qui interagit avec le complexe récepteur aux lipopolysaccharides [14]. Des taux plus élevés de LBP ont été rapportés chez des sujets en surpoids et obèses [32][33][34]. Ils pourraient être liés à l'inflammation systémique de bas grade que l'on observe chez ces sujets.…”

Evaluation of the use of the Endotoxin Activity Assay (EAA™) to Quantify Non-septic Exposure of Metabolic Endotoxemia

“…The LBP has been used extensively to detect low levels of metabolic endotoxemia associated with obesity [5][6][7][8][9]. LBP has been used to detect varying levels of endotoxemia in inflammatory bowel conditions, pancreatitis, cirrhosis and sepsis where levels in serum can increase 10 to 50 fold during acute inflammation [10,11].…”