title: Gamma-synuclein is an adipocyte-neuron gene coordinately expressed with leptin and increased in human obesity.
abstract: Recently, we characterized tumor suppressor candidate 5 (Tusc5) as an adipocyte-neuron PPARgamma 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 adipogenesis 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 approximately 50% following treatment with the PPARgamma 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 approximately 1.7-fold in obese Pima Indian adipocytes (P = 0.003) and approximately 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 adipocyte physiology.
authors.affiliation: USDA/Agricultural Research Service Western Human Nutrition Research Center, Davis, CA 95616, USA.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Oort
authors.forename: Trina A
authors.initials: TA
authors.lastname: Knotts
authors.forename: Michel
authors.initials: M
authors.lastname: Grino
authors.forename: Nadia
authors.initials: N
authors.lastname: Naour
authors.forename: Jean-Phillipe
authors.initials: JP
authors.lastname: Bastard
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Natalia
authors.initials: N
authors.lastname: Ninkina
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Buchman
authors.forename: Paska A
authors.initials: PA
authors.lastname: Permana
authors.forename: Xunyi
authors.initials: X
authors.lastname: Luo
authors.forename: Guohua
authors.initials: G
authors.lastname: Pan
authors.forename: Tamara N
authors.initials: TN
authors.lastname: Dunn
authors.forename: Sean H
authors.initials: SH
authors.lastname: Adams
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000737:chemistry / Q000166:cytology; D000273:Adipose Tissue / Q000737:chemistry*; D000818:Animals; D001577:Benzophenones / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007198:Indians, North American; D020738:Leptin / Q000235:genetics*; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists; D017933:Peripheral Nervous System / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D051845:gamma-Synuclein / Q000032:analysis / Q000235:genetics*
chemical_list: D001577:Benzophenones; D020738:Leptin; D047495:PPAR gamma; D012333:RNA, Messenger; D051845:gamma-Synuclein; D014443:Tyrosine; C120099:GW 1929