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

CONTEXT: Nerve growth factor (NGF) affects the development and survival of sympathetic neurons. 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. METHODS: The expression of NGF and its receptors, tropomyosin-related kinase A (TrkA) and pan-neurotrophin receptor (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, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, and adiponectin levels. Additionally, NGF increased lipolysis in human WAT explants and suppressed lipids accumulation, lipoprotein lipase, and pro-inflammatory mediators interleukin (IL)-6 and IL-8 in human white adipocytes. The pro-inflammatory factor lipopolysaccharide downregulated 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. CONCLUSION: Our data suggest that NGF is produced locally within the adipose tissue where it upregulates mitochondrial function while it suppresses the pro-inflammatory phenotype of human and mouse adipocytes.