NGF promotes, in an autocrine-paracrine manner, metabolic and anti-inflammatory pathways in human and mouse adipocytes

Abstract Context Nerve Growth Factor (NGF) affects sympathetic neurons’ development and survival. NGF is also found in non-neural cell lineages that are implicated in immune-endocrine interactions associated with metabolic diseases. Although NGF is expressed in white adipose tissue (WAT), little is known about the regulation of its expression and role in adipocytes. Objective To determine whether NGF and its receptors are expressed in human adipocytes and demonstrate their role in adipocyte metabolic and inflammatory phenotypes. Design The expression of NGF and its receptors TrkA and p75NTR and their effects on metabolic and inflammatory responses were examined in freshly isolated adipocytes from human abdominal WAT and mouse 3T3L1 cells. Results TrkA and p75NTR were expressed in both human and mouse adipocytes and pre-adipocytes. NGF was secreted by human white adipocytes and their exogenous exposure to NGF increased mitochondrial mass and activity, PPAR-gamma, CEBPA and adiponectin levels. Additionally, NGF increased lipolysis in human WAT explants and suppressed lipids accumulation, LPL and pro-inflammatory mediators IL-6 and IL-8 in human white adipocytes. The pro-inflammatory factor LPS down-regulated the levels of NGF receptors in human white adipocytes. NGF also affected mitochondrial activity in both human and mouse pre-adipocytes and TrkA appeared to mediate, at least partially, the effects of NGF on adipocytes. Conclusions Our data suggests that NGF is produced locally within the adipose tissue where it up-regulates mitochondrial function while it suppresses the pro-inflammatory phenotype of human and mouse adipocytes.