Research ArticleMETABOLIC DISEASE

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

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Science Immunology  16 Mar 2018:
Vol. 3, Issue 21, eaan4626
DOI: 10.1126/sciimmunol.aan4626

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Keeping the calm in the adipose tissue

Obesity is associated with chronic inflammation and accumulation of immune cells in adipose tissue. Here, Wilson et al. report that macrophages that express neuropilin-1 (NRP1) play an essential role in limiting obesity-associated inflammation. In mice placed on a high-fat diet, deletion of NRP1 in myeloid cells accelerated both weight gain and development of insulin resistance. The authors found that NRP1 regulated fatty acid uptake in macrophages and that deficiency of NRP1 skewed their metabolism toward glycolysis, which is associated with a more aggressive inflammation. The studies add to the growing recognition of the importance of immune cells in obesity and other metabolic syndromes.

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.

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