Evaluation of the Synuclein-gamma (SNCG) Gene as a PPAR gamma Target in Murine Adipocytes, Dorsal Root Ganglia Somatosensory Neurons, and Human Adipose Tissue Article

Open Access International Collaboration

cited authors

  • Dunn, Tamara N., Akiyama, Tasuku, Lee, Hyun Woo, Kim, Jae Bum, Knotts, Trina A., Smith, Steven R., Sears, Dorothy D., Carstens, Earl, Adams, Sean H.

funding text

  • This work was funded in part by the following: intramural USDA-ARS Projects [530651530-016-00D] and [5306-51530-019-00D] (S.H.A.), the Vitamin Cases Consumer Settlement Fund [CHNR08-801] (to S.H.A.), an unrestricted grant from Takeda Pharmaceuticals North America (to S.R.S.), and a grant from the Korean government (Ministry of Education, Science, and Technology [2012-0001241], to J.B.K.). The USDA is an equal opportunity provider and employer.

abstract

  • Recent evidence in adipocytes points to a role for synuclein-gamma in metabolism and lipid droplet dynamics, but interestingly this factor is also robustly expressed in peripheral neurons. Specific regulation of the synuclein-gamma gene (Sncg) by PPAR gamma requires further evaluation, especially in peripheral neurons, prompting us to test if Sncg is a bona fide PPAR gamma target in murine adipocytes and peripheral somatosensory neurons derived from the dorsal root ganglia (DRG). Sncg mRNA was decreased in 3T3-L1 adipocytes (similar to 68%) by rosiglitazone, and this effect was diminished by the PPAR gamma. antagonist T0070907. Chromatin immunoprecipitation experiments confirmed PPAR gamma protein binding at two promoter sequences of Sncg during 3T3-L1 adipogenesis. Rosiglitazone did not affect Sncg mRNA expression in murine cultured DRG neurons. In subcutaneous human WAT samples from two cohorts treated with pioglitazone (> 11 wks), SNCG mRNA expression was reduced, albeit highly variable and most evident in type 2 diabetes. Leptin (Lep) expression, thought to be coordinately-regulated with Sncg based on correlations in human adipose tissue, was also reduced in 3T3-L1 adipocytes by rosiglitazone. However, Lep was unaffected by PPAR. antagonist, and the LXR agonist T0901317 significantly reduced Lep expression (similar to 64%) while not impacting Sncg. The results support the concept that synuclein-gamma shares some, but not all, gene regulators with leptin and is a PPAR gamma target in adipocytes but not DRG neurons. Regulation of synuclein-gamma by cues such as PPAR gamma agonism in adipocytes is logical based on recent evidence for an important role for synuclein-gamma in the maintenance and dynamics of adipocyte lipid droplets.

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Publication Date

  • March 10, 2015

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volume

  • 10

issue

  • 3

WoS Citations

  • 8

WoS References

  • 64