PMID- 21738950 OWN - NLM STAT- MEDLINE DCOM- 20120803 LR - 20220410 IS - 1528-3658 (Electronic) IS - 1076-1551 (Print) IS - 1076-1551 (Linking) VI - 17 IP - 11-12 DP - 2011 TI - Increased levels of calprotectin in obesity are related to macrophage content: impact on inflammation and effect of weight loss. PG - 1157-67 LID - 10.2119/molmed.2011.00144 [doi] AB - 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 alpha-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-alpha 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. FAU - Catalan, Victoria AU - Catalan V AD - Metabolic Research Laboratory, Clinica Universidad de Navarra, Pamplona, Spain. FAU - Gomez-Ambrosi, Javier AU - Gomez-Ambrosi J FAU - Rodriguez, Amaia AU - Rodriguez A FAU - Ramirez, Beatriz AU - Ramirez B FAU - Rotellar, Fernando AU - Rotellar F FAU - Valenti, Victor AU - Valenti V FAU - Silva, Camilo AU - Silva C FAU - Gil, Maria J AU - Gil MJ FAU - Fernandez-Real, Jose Manuel AU - Fernandez-Real JM FAU - Salvador, Javier AU - Salvador J FAU - Fruhbeck, Gema AU - Fruhbeck G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110705 PL - England TA - Mol Med JT - Molecular medicine (Cambridge, Mass.) JID - 9501023 RN - 0 (Leukocyte L1 Antigen Complex) RN - 0 (Protein Subunits) RN - 0 (RNA, Messenger) RN - 0 (Receptor for Advanced Glycation End Products) RN - 0 (Receptors, Immunologic) RN - 0 (S100 Proteins) RN - 0 (S100A1 protein) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adipocytes/metabolism/pathology MH - Adult MH - Anthropometry MH - Diabetes Mellitus, Type 2/blood/complications MH - Female MH - Gene Expression Regulation MH - Humans MH - Inflammation/blood/*complications/pathology MH - Intra-Abdominal Fat/metabolism/pathology MH - Leukocyte L1 Antigen Complex/*blood/genetics MH - Macrophages/*metabolism/pathology MH - Obesity/*blood/complications MH - Protein Subunits/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - Receptor for Advanced Glycation End Products MH - Receptors, Immunologic/blood MH - S100 Proteins/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - *Weight Loss/genetics PMC - PMC3321803 EDAT- 2011/07/09 06:00 MHDA- 2012/08/04 06:00 PMCR- 2011/07/05 CRDT- 2011/07/09 06:00 PHST- 2011/04/19 00:00 [received] PHST- 2011/06/30 00:00 [accepted] PHST- 2011/07/09 06:00 [entrez] PHST- 2011/07/09 06:00 [pubmed] PHST- 2012/08/04 06:00 [medline] PHST- 2011/07/05 00:00 [pmc-release] AID - molmed.2011.00144 [pii] AID - 11_144_catalan [pii] AID - 10.2119/molmed.2011.00144 [doi] PST - ppublish SO - Mol Med. 2011;17(11-12):1157-67. doi: 10.2119/molmed.2011.00144. Epub 2011 Jul 5.