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Diabetes. 2014 Dec;63(12):4143-53. doi: 10.2337/db14-0256. Epub 2014 Jul 9.

Mannose-binding lectin is required for the effective clearance of apoptotic cells by adipose tissue macrophages during obesity.

Author information

  • 1Nutrition, 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.
  • 2Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen, the Netherlands.
  • 3Department of Human Genetics, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
  • 4Department of Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.
  • 5Laboratory of Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, the Netherlands.

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.

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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