title: Increased levels of calprotectin in obesity are related to macrophage content: impact on inflammation and effect of weight loss.
abstract: Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage-related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin α-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-α treatment significantly enhanced (P < 0.05) the mRNA levels of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The increased levels of calprotectin in obesity and obesity-associated type 2 diabetes, its positive association with inflammation as well as the higher expression levels in the SVFCs in VAT suggests a potential role of this protein as a chemotactic factor in the recruitment of macrophages to VAT, increasing inflammation and the development of obesity-associated comorbidities.
authors: Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.
authors: Victoria
authors: V
authors: Catalán
authors: Javier
authors: J
authors: Gómez-Ambrosi
authors: Amaia
authors: A
authors: Rodríguez
authors: Beatriz
authors: B
authors: Ramírez
authors: Fernando
authors: F
authors: Rotellar
authors: Victor
authors: V
authors: Valentí
authors: Camilo
authors: C
authors: Silva
authors: María J
authors: MJ
authors: Gil
authors: José Manuel
authors: JM
authors: Fernández-Real
authors: Javier
authors: J
authors: Salvador
authors: Gema
authors: G
authors: Frühbeck
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000886:Anthropometry; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000378:metabolism / Q000473:pathology; D039841:Leukocyte L1 Antigen Complex / Q000097:blood* / Q000235:genetics; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000097:blood* / Q000150:complications; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D009418:S100 Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss / Q000235:genetics
chemical_list: D039841:Leukocyte L1 Antigen Complex; D021122:Protein Subunits; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; C110294:S100A1 protein; D014409:Tumor Necrosis Factor-alpha