Plasma neuropilin-1 is associated with a favorable lipid profile and insulin sensitivity in a population-based sample of 50-year-old individuals.

Membrane-bound neuropilin-1 (Nrp-1) has been implicated as a regulator of insulin resistance-related lipid metabolism, but little is known about its circulating form, soluble Nrp-1 (sNrp-1), in a metabolic context. Here we investigated the association between plasma levels of sNrp-1 and metabolic variables in 501 participants from the Prospective investigation of Obesity, Energy and Metabolism (POEM) study. Metabolic phenotyping included blood sampling, dual energy X-ray absorptiometry scan, magnetic resonance imaging for fat distribution, and a glucose tolerance test. Associations were examined using linear regression models and Spearman's rank correlation. Plasma sNrp-1 levels were inversely associated with levels of total fatty acids, triglycerides and lactate, and positively associated with markers of insulin sensitivity. In human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes, we showed that treatment with recombinant Nrp-1 reduced phosphorylation of hormone-sensitive lipase in the basal state and attenuated isoproterenol-stimulated glycerol release, a measure of total lipolytic activity. Based on these findings, we thus postulate that sNrp-1-mediated suppression of lipolysis could explain our observed association between plasma sNrp-1 and a favorable lipid profile in humans. Further studies are warranted to establish causality and to clarify the role of sNrp-1 in promoting insulin sensitivity in human adipose tissue.