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

• Published in: International Journal of Obesity Vol. 36; no. 11; pp. 1442 - 1449
• Main Authors: Moreno-Navarrete, J M, Ortega, F, Serino, M, Luche, E, Waget, A, Pardo, G, Salvador, J, Ricart, W, Frühbeck, G, Burcelin, R, Fernández-Real, J M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2012; Nature Publishing Group
• Subjects: 631/45/287/1190; 692/53; 692/699/2743/393; 692/699/317; Acute-Phase Proteins - metabolism; Adipose Tissue; Analysis; Animals; Binding proteins; Biological and medical sciences; Biomarkers - blood; Blood; Body Mass Index; Carrier Proteins - blood; Complications and side effects; Cross-Sectional Studies; Diabetes; Diet; Endocrinology; Enzyme-Linked Immunosorbent Assay; Epidemiology; Female; Glucagon; Glucose; Health Promotion and Disease Prevention; Humans; Immune system; Inflammation - blood; Insulin Resistance; Internal Medicine; Lipids; Male; Medical sciences; Medicine; Medicine & Public Health; Membrane Glycoproteins - blood; Metabolic Diseases; Metabolism; Mice; Nutrition research; Obesity; Obesity - blood; original-article; Peptides; Physiological aspects; Plasma; Proteins; Public Health; Risk factors; Spain; Systemic diseases; Weight control; Weight Loss; White people; Spain; insulin resistance; LPS; LBP; Endocrinopathy; Human; Obesity; Pancreatic hormone; Nutrition; Rodentia; Nutrition disorder; Biological marker; Metabolic diseases; Protein A; Insulin; Binding protein; Target tissue resistance; Vertebrata; Mammalia; Mouse; Lipopolysaccharide; Insulin resistance; Nutritional status
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/ijo.2011.256

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 =222) and weight loss-induced ( n =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 μg ml −1 , P <0.0001) 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.