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1 Neuroendocrine and Obesity Biology Unit, Liverpool Centre for Nutritional Genomics, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom
2 Neuroendocrine and Obesity Biology Unit, Liverpool Centre for Nutritional Genomics, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom; The Henry Wellcome Laboratory of Molecular and Cellular Gastroenterology, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom
* To whom correspondence should be addressed. E-mail: p.trayhurn{at}liverpool.ac.uk.
The sympathetic nervous system plays a central role in lipolysis and the production of leptin in white adipose tissue (WAT). In this study we have examined whether nerve growth factor (NGF), a target-derived neurotrophin that is a key signal in the development and survival of sympathetic neurones, is expressed and secreted by white adipocytes. NGF mRNA was detected by RT-PCR in the major WAT depots of mice (epididymal, perirenal, omental, mesenteric, subcutaneous) and in human fat (subcutaneous, omental). In mouse WAT, NGF expression was observed in mature adipocytes and in stromal-vascular cells. NGF expression was also evident in 3T3-L1 cells, before and after differentiation into adipocytes. NGF protein, measured by ELISA, was secreted from 3T3-L1 cells, release being higher pre-differentiation. Addition of the sympathetic agonists norepinephrine, isoprenaline or BRL 37344 (
3-agonist) led to falls in NGF gene expression and secretion by 3T3-L1 adipocytes, as did IL-6 and the PPAR
agonist, rosiglitazone. A substantial decrease in NGF expression and secretion occurred with dexamethasone. In contrast, lipopolysaccharide increased NGF mRNA levels and NGF secretion. A major increase in NGF mRNA level (9-fold) and NGF secretion (up to 40-fold) in 3T3-L1 adipocytes occurred with TNF
. RT-PCR showed that the genes encoding the p75 and trkA NGF receptors were expressed in mouse WAT. These results demonstrate that white adipocytes secrete NGF (an adipokine), NGF synthesis being influenced by several factors with TNF having a major stimulatory effect. We suggest that NGF is a target-derived neurotrophin and an inflammatory response protein in white adipocytes.
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