Myeloid cell neuropilin 1 ameliorates high-fat diet-induced insulin resistance via suppression of Nlrp3 inflammasome

Abstract

The history of neuropilin 1 (Nrp1) research is checkered with many unexpected and exciting findings. Nrp1 functions as a co-receptor for class 3 semaphorins, and several canonical growth factors, including vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). It has been implicated in the development of central nervous system, angiogenesis, and migration. Accumulating evidence demonstrates that Nrp1 is also highly expressed in immune cells, including macrophages and dendritic cells. Until now, the functions of Nrp1 within these cells remained poorly studied and elusive. Here, we provide exciting insights on a novel role for myeloid cell Nrp1 in the mitigation of dietary insulin resistance through inhibiting Nlrp3 inflammasome. Keywords neuropilin 1; Nlrp3 inflammasome; insulin resistance Globally, obesity has become a critical public health problem, and is closely associated with insulin resistance [1]. In a classic sequence of cellular events, macrophages infiltrate insulin sensitive tissues, instigate inflammation, and lead to insulin resistance [2]. Therefore, tissue macrophages represent a major contributor of metabolic diseases, and macrophage regulation may indeed present opportunities at protecting against these conditions. Although Nrp1 was originally identified in neuronal and endothelial cells, it was later discovered to be highly expressed in macrophages [3]. Subsequently, it was demonstrated that Sema3A/Nrp1 signaling was critical to the entry of macrophages into hypoxic tumor areas, where recruited tumor-associated macrophages promoted angiogenesis, impaired antitumor immunity and resulted in tumor growth [4]. Pro-tumorigenic effect of macrophage Nrp1 has been recently confirmed in another tumor model, Gliomas [5]. However, the roles Licensed under a Creative Commons Attribution 4.0 International License which allows users including authors of articles to copy and redistribute the material in any medium or format, in addition to remix, transform, and build upon the material for any purpose, even commercially, as long as the author and original source are properly cited or credited.