title: Mannose-binding lectin is required for the effective clearance of apoptotic cells by adipose tissue macrophages during obesity.
abstract: Obesity is accompanied by the presence of chronic low-grade inflammation manifested by infiltration of macrophages into adipose tissue. Mannose-binding lectin (MBL), a soluble mediator of innate immunity, promotes phagocytosis and alters macrophage function. To assess the function of MBL in the development of obesity, we studied wild-type and MBL(-/-) mice rendered obese using a high-fat diet (HFD). Whereas no gross morphological differences were observed in liver, an HFD provoked distinct changes in the adipose tissue morphology of MBL(-/-) mice. In parallel with increased adipocyte size, MBL(-/-) mice displayed an increased influx of macrophages into adipose tissue. Macrophages were polarized toward an alternatively activated phenotype known to modulate apoptotic cell clearance. MBL deficiency also significantly increased the number of apoptotic cells in adipose tissue. Consistent with these observations, recombinant MBL enhanced phagocytic capacity of the stromal vascular fraction isolated from adipose tissue and modulated uptake of apoptotic adipocytes by macrophages. Despite changes in macrophage abundance and polarity, the absence of MBL did not affect systemic insulin resistance. Finally, in humans, lower levels of circulating MBL were accompanied by enhanced macrophage influx in subcutaneous adipose tissue. We propose a novel role for MBL in the recognition and clearance of apoptotic adipocytes during obesity.
authors.affiliation: Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen, the Netherlands Department of Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Radboud University Medical Centre, Nijmegen, the Netherlands rinke.stienstra@wur.nl.
authors.forename: Rinke
authors.initials: R
authors.lastname: Stienstra
authors.affiliation: Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen, the Netherlands.
authors.forename: Wieneke
authors.initials: W
authors.lastname: Dijk
authors.affiliation: Department of Human Genetics, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Lianne
authors.initials: L
authors.lastname: van Beek
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Henry
authors.initials: H
authors.lastname: Jansen
authors.affiliation: Department of Human Genetics, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Mattijs
authors.initials: M
authors.lastname: Heemskerk
authors.affiliation: Laboratory of Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Riekelt H
authors.initials: RH
authors.lastname: Houtkooper
authors.affiliation: Laboratory of Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Denis
authors.affiliation: Department of Human Genetics, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Vanessa
authors.initials: V
authors.lastname: van Harmelen
authors.affiliation: Department of Human Genetics, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ko
authors.initials: K
authors.lastname: Willems van Dijk
authors.affiliation: Department of Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Tack
authors.affiliation: Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen, the Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kersten
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D050177:Overweight / Q000209:etiology / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics*
chemical_list: D037601:Mannose-Binding Lectin