PMID- 27221527 OWN - NLM STAT- MEDLINE DCOM- 20170707 LR - 20181202 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 24 IP - 7 DP - 2016 Jul TI - Osteopontin affects macrophage polarization promoting endocytic but not inflammatory properties. PG - 1489-98 LID - 10.1002/oby.21510 [doi] AB - OBJECTIVE: Macrophages are the main drivers of obesity-induced adipose tissue (AT) inflammation that causes insulin resistance. Macrophages polarize toward different inflammatory (M1) or protective (M2) phenotypes. Osteopontin (OPN) is an inflammatory cytokine highly expressed in AT in obesity and known to be involved in chronic inflammatory processes. It was hypothesized that OPN polarizes macrophages into a proinflammatory phenotype. METHODS: AT macrophages (ATMs) of OPN-deficient (Spp1(-/-) ) and wild-type C57BL/6 (WT) mice with obesity and bone marrow-derived macrophages (BMDMs) of Spp1(-/-) and WT mice as well as human monocyte-derived macrophages (MDMs) polarized in the presence of OPN were investigated. RESULTS: While ATM infiltration was lower in Spp1(-/-) upon high-fat diet, Spp1(-/-) ATMs expressed more M1 and less M2 markers but less tumor necrosis factor-alpha compared with WT. There was no effect of OPN deficiency on BMDM polarization. In human MDMs, the presence of OPN during polarization ambiguously altered M1/M2-related marker expression and diminished LPS-induced inflammatory cytokine production. Strikingly, phagocytic activity was elevated by the presence of OPN during polarization in both human MDMs and murine BMDMs. CONCLUSIONS: In contradiction to our hypothesis, data indicated that OPN does not induce inflammatory macrophages but was a signal to induce phagocytosis, which may be required due to increased adipocyte death in obesity. CI - (c) 2016 The Obesity Society. FAU - Schuch, Karina AU - Schuch K AD - Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. AD - Department of Health, Section Biomedical Science, FH Campus Wien, University of Applied Sciences, Vienna, Austria. FAU - Wanko, Bettina AU - Wanko B AD - Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. FAU - Ambroz, Katharina AU - Ambroz K AD - Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. AD - Department of Health, Section Biomedical Science, FH Campus Wien, University of Applied Sciences, Vienna, Austria. FAU - Castelo-Rosa, Alexandra AU - Castelo-Rosa A AD - Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. AD - Department of Health, Section Biomedical Science, FH Campus Wien, University of Applied Sciences, Vienna, Austria. FAU - Moreno-Viedma, Veronica AU - Moreno-Viedma V AD - Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. FAU - Grun, Nicole G AU - Grun NG AD - Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. FAU - Leitner, Lukas AU - Leitner L AD - Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. FAU - Staffler, Gunther AU - Staffler G AD - AFFiRiS AG, Vienna, Austria. FAU - Zeyda, Maximilian AU - Zeyda M AD - Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. AD - Department of Pediatrics and Adolescent Medicine, Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Medical University of Vienna, Vienna, Austria. FAU - Stulnig, Thomas M AU - Stulnig TM AD - Department of Medicine III, Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria. LA - eng PT - Journal Article DEP - 20160525 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Tumor Necrosis Factor-alpha) RN - 106441-73-0 (Osteopontin) SB - IM MH - Adipocytes/physiology MH - Adipose Tissue/metabolism MH - Animals MH - Diet, High-Fat MH - Inflammation/physiopathology MH - Insulin Resistance MH - Macrophages/*physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Obesity/*physiopathology MH - Osteopontin/*metabolism MH - Phagocytosis/physiology MH - Phenotype MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2016/05/26 06:00 MHDA- 2017/07/08 06:00 CRDT- 2016/05/26 06:00 PHST- 2015/12/21 00:00 [received] PHST- 2016/02/29 00:00 [revised] PHST- 2016/03/04 00:00 [accepted] PHST- 2016/05/26 06:00 [entrez] PHST- 2016/05/26 06:00 [pubmed] PHST- 2017/07/08 06:00 [medline] AID - 10.1002/oby.21510 [doi] PST - ppublish SO - Obesity (Silver Spring). 2016 Jul;24(7):1489-98. doi: 10.1002/oby.21510. Epub 2016 May 25.