γ-Synuclein is an adipocyte-neuron gene coordinately expressed with leptin and increased in human obesity

Recently, we characterized tumor suppressor candidate 5 (Tusc5) as an adipocyte-neuron PPAR gamma target gene. Our objective herein was to identify additional genes that display distinctly high expression in fat and neurons, because such a pattern could signal previously uncharacterized functional pathways shared in these disparate tissues. gamma-Synuclein, a marker of peripheral and select central nervous system neurons, was strongly expressed in white adipose tissue (WAT) and peripheral nervous system ganglia using bioinformatics and quantitative PCR approaches. gamma-Synuclein expression was determined during ad;pogenesis and in subcutaneous (SC) and visceral adipose tissue (VAT) from obese and nonobese humans. gamma-Synuclein mRNA increased from trace levels in preadipocytes to high levels in mature 3T3-L1 adipocytes and decreased similar to 50% following treatment with the PPAR gamma agonist GW1929 (P < 0.01). Because gamma-synuclein limits growth arrest and is implicated in cancer progression in nonadipocytes, we suspected that expression would be increased in situations where WAT plasticity/adipocyte turnover are engaged. Consistent with this postulate, human WAT gamma-synuclein mRNA levels consistently increased in obesity and were higher in SC than in VAT; i.e. they increased similar to 1.7-fold in obese Pima Indian adipocytes (P = 0.003) and similar to 2-fold in SC and VAT of other obese cohorts relative to nonobese subjects. Expression correlated with leptin transcript levels in human SC and VAT (r = 0.887; P < 0.0001; n = 44). gamma-Synuclein protein was observed in rodent and human WAT but not in negative control liver. These results are consistent with the hypothesis that gamma-synuclein plays an important role in adipocyle physiology.