Circulating lipopolysaccharide-binding protein (LBP) as a marker of obesity-related insulin resistance

Abstract

OBJECTIVE: Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute-phase protein present in blood at high concentrations, known to be derived from the liver. We aimed to gain insights into the association of circulating LBP with insulin resistance in humans and mice. METHODS, DESIGN AND MEASUREMENTS: We studied the cross-sectional (n ¼ 222) and weight loss-induced (n ¼ 34) associations of LBP (enzyme-linked immunosorbent assay) with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity), and the effects of high-fat diet (HFD), metformin and genetic insulin sensitization (glucagon-like peptide 1 receptor knockout model) in mice. RESULTS: Circulating LBP concentration was significantly increased in subjects with type 2 diabetes and dramatically increased in subjects with morbid obesity. LBP was significantly associated with insulin sensitivity and different inflammatory markers and decreased after weight loss (22.2 ± 5.8 vs 16.2 ± 9.3 mg ml À1 , Po0.0001) in association with changes in body mass index and insulin sensitivity. Circulating LBP concentration was increased in HFD mice, whereas decreased in glucagon-like peptide 1 receptor knockout mice (significantly more insulin sensitive than wild-type mice) and after metformin administration. CONCLUSION: LBP is an inflammatory marker associated with obesity-related insulin resistance.

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

“…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].…”

“…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]. 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].…”

“…LBP levels, serum glucose, HbA 1c , serum insulin, total cholesterol, HDL-cholesterol, LDL-cholesterol and total serum triacylglycerols were measured as previously described [18]. See ESM Methods for further details.…”

“…All the animal experimental procedures to test the effects of a high-fat diet and LPS were studied using mesenteric white AT (WAT). They were approved by the local ethics committee of the Rangueil Hospital, Toulouse, France and were performed as previously described [4,18,25,26].…”

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.…”