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 PPARγ 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. γ-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. γ-Synuclein expression was determined during adipogenesis and in subcutaneous (SC) and visceral adipose tissue (VAT) from obese and nonobese humans. γ-Synuclein mRNA increased from trace levels in preadipocytes to high levels in mature 3T3-L1 adipocytes and decreased ∼50% following treatment with the PPARγ agonist GW1929 (P < 0.01). Because "y-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 γ-synuclein mRNA levels consistently increased in obesity and were higher in SC than in VAT; i.e. they increased ∼1.7-fold in obese Pima Indian adipocytes (P - 0.003) and ∼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). γ-Synuclein protein was observed in rodent and human WAT but not in negative control liver. These results are consistent with the hypothesis that γ-synuclein plays an important role in adipocyte physiology.