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

Published on Dec 1, 2014in Diabetes7.199
· DOI :10.2337/db14-0256
Rinke Stienstra31
Estimated H-index: 31
(Radboud University Nijmegen),
Wieneke Dijk10
Estimated H-index: 10
(WUR: Wageningen University and Research Centre)
+ 8 AuthorsSander Kersten67
Estimated H-index: 67
(WUR: Wageningen University and Research Centre)
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.
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National Cancer Institute grants RO1 01CA170549-02 (to D. Panigrahy and C.N. Serhan), ROCA148633-01A4 (to D. Panigrahy), and GM095467 (to C.N. Serhan); the Stop and Shop Pediatric Brain Tumor Fund (to M.W. Kieran); the CJ Buckley Pediatric Brain Tumor Fund (to M.W. Kieran); Alex Lemonade Stand (to M.W. Kieran); Molly’s Magic Wand for Pediatric Brain Tumors (to M.W. Kieran); the Markoff Foundation Art-In-Giving Foundation (to M.W. Kieran); the Kamen Foundation (to M.W. Kieran); Jared Branfman Sun...
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