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Sci Immunol. 2018 Mar 16;3(21). pii: eaan4626. doi: 10.1126/sciimmunol.aan4626.

Neuropilin-1 expression in adipose tissue macrophages protects against obesity and metabolic syndrome.

Author information

1
Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec H1T 2M4, Canada.
2
Department of Engineering Physics, École Polytechnique de Montréal, Montreal, Quebec H3T 1J4, Canada.
3
Department of Microbiology, Infectiology and Immunology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec H1T 2M4, Canada.
4
Department of Ophthalmology, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec H1T 2M4, Canada.
5
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Université Laval, Faculté de médecine, 2725 Chemin Ste-Foy, Quebec, Quebec G1V 4G5, Canada.
6
Montreal Heart Institute, Université de Montréal, Montreal, Quebec H1T 1C8, Canada.
7
Institut de la Vision, Institut National de la Santé et de la Recherche Médicale, U 968, Paris F-75012, France.
8
Departments of Pediatrics, Ophthalmology, and Pharmacology, Centre Hospitalier Universitaire Ste-Justine Research Center, Université de Montréal, Montreal, Quebec H1T 2M4, Canada.
9
Department of Biochemistry, Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Quebec H1T 2M4, Canada. mike.sapieha@umontreal.ca.

Abstract

Obesity gives rise to metabolic complications by mechanisms that are poorly understood. Although chronic inflammatory signaling in adipose tissue is typically associated with metabolic deficiencies linked to excessive weight gain, we identified a subset of neuropilin-1 (NRP1)-expressing myeloid cells that accumulate in adipose tissue and protect against obesity and metabolic syndrome. Ablation of NRP1 in macrophages compromised lipid uptake in these cells, which reduced substrates for fatty acid β-oxidation and shifted energy metabolism of these macrophages toward a more inflammatory glycolytic metabolism. Conditional deletion of NRP1 in LysM Cre-expressing cells leads to inadequate adipose vascularization, accelerated weight gain, and reduced insulin sensitivity even independent of weight gain. Transfer of NRP1+ hematopoietic cells improved glucose homeostasis, resulting in the reversal of a prediabetic phenotype. Our findings suggest a pivotal role for adipose tissue-resident NRP1+-expressing macrophages in driving healthy weight gain and maintaining glucose tolerance.

PMID:
29549139
DOI:
10.1126/sciimmunol.aan4626
[Indexed for MEDLINE]

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