Mannose-Binding Lectin is required for the effective clearance of apoptotic cells by adipose tissue macrophages during obesity

  1. Sander Kersten1
  1. 1Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen 6703 HD, The Netherlands
  2. 2Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen 6525 GA, The Netherlands
  3. 3Nijmegen Institute for Infection, Inflammation and Immunity (N4I), Radboud University Nijmegen Medical Centre, Nijmegen 6525 GA, The Netherlands
  4. 4Department of Human Genetics, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
  5. 5Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands
  1. *Corresponding author: Rinke Stienstra, Email: Rinke.Stienstra{at}wur.nl

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 WT and MBL-/- mice rendered obese by high fat feeding (HFD). Whereas no gross morphological differences were observed in liver, HFD feeding provoked distinct changes in adipose tissue morphology of MBL-/- mice. In parallel with increased adipocyte size, MBL-/- mice displayed increased influx of macrophages into adipose tissue. Macrophages were polarized towards 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, absence of MBL did not impact 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 recognition and clearance of apoptotic adipocytes during obesity.

  • Received February 14, 2014.
  • Accepted June 26, 2014.

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