title: Evaluation of the synuclein-γ (SNCG) gene as a PPARγ target in murine adipocytes, dorsal root ganglia somatosensory neurons, and human adipose tissue.
abstract: Recent evidence in adipocytes points to a role for synuclein-γ in metabolism and lipid droplet dynamics, but interestingly this factor is also robustly expressed in peripheral neurons. Specific regulation of the synuclein-γ gene (Sncg) by PPARγ requires further evaluation, especially in peripheral neurons, prompting us to test if Sncg is a bona fide PPARγ target in murine adipocytes and peripheral somatosensory neurons derived from the dorsal root ganglia (DRG). Sncg mRNA was decreased in 3T3-L1 adipocytes (~68%) by rosiglitazone, and this effect was diminished by the PPARγ antagonist T0070907. Chromatin immunoprecipitation experiments confirmed PPARγ 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 PPARγ antagonist, and the LXR agonist T0901317 significantly reduced Lep expression (~64%) while not impacting Sncg. The results support the concept that synuclein-γ shares some, but not all, gene regulators with leptin and is a PPARγ target in adipocytes but not DRG neurons. Regulation of synuclein-γ by cues such as PPARγ agonism in adipocytes is logical based on recent evidence for an important role for synuclein-γ in the maintenance and dynamics of adipocyte lipid droplets.
authors.affiliation: Graduate Group in Nutritional Biology, University of California Davis, Davis, California, United States of America; Department of Nutrition, University of California Davis, Davis, California, United States of America.
authors.forename: Tamara N
authors.initials: TN
authors.lastname: Dunn
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, California, United States of America.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: National Creative Research Initiatives Center for Adipose Tissue Remodeling, Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: National Creative Research Initiatives Center for Adipose Tissue Remodeling, Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Department of Nutrition, University of California Davis, Davis, California, United States of America; Arkansas Children's Nutrition Center and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Trina A
authors.initials: TA
authors.lastname: Knotts
authors.affiliation: Sanford-Burnham Medical Research Institute and Translational Research Institute, Florida Hospital, Orlando, Florida, United States of America.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Dorothy D
authors.initials: DD
authors.lastname: Sears
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, California, United States of America.
authors.forename: Earl
authors.initials: E
authors.lastname: Carstens
authors.affiliation: Graduate Group in Nutritional Biology, University of California Davis, Davis, California, United States of America; Department of Nutrition, University of California Davis, Davis, California, United States of America; Arkansas Children's Nutrition Center and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Sean H
authors.initials: SH
authors.lastname: Adams
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D047495:PPAR gamma / Q000819:agonists / Q000502:physiology*; D000077205:Pioglitazone; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000077154:Rosiglitazone; D011984:Sensory Receptor Cells; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D051845:gamma-Synuclein / Q000235:genetics*
chemical_list: D007004:Hypoglycemic Agents; D009363:Neoplasm Proteins; D047495:PPAR gamma; C104249:SNCG protein, human; D045162:Thiazolidinediones; D051845:gamma-Synuclein; D000077154:Rosiglitazone; D000077205:Pioglitazone