title: Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats.
abstract: OBJECTIVE
  The effects of the proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone (ROSI) on the transforming growth factor (TGF)-β/SMAD signaling pathway in white adipose tissue (WAT) of diabetic rats were assessed.
  
  
  METHODS
  Six-week-old, male ZDF rats were fed a chow diet with (ZDF ROSI) or without (ZDF chow) ROSI (diet, 100 mg/kg) for 6 weeks. Subcutaneous (scWAT) and retroperitoneal (rpWAT) adipose tissues were excised to quantify the protein content/phosphorylation.
  
  
  RESULTS
  ZDF ROSI animals showed enhanced glucose tolerance and mitochondrial protein content in both depots. The protein content of enzymes involved in fatty acid handling was increased in scWAT of ZDF ROSI animals. ZDF ROSI exhibited decreased phosphorylation of SMAD2 and SMAD3 exclusively in scWAT, along with increases in inhibitory SMAD7 and the E3 ubiquitin ligase SMURF2. In contrast, ROSI increased the protein content of SMAD4, TGF-β receptor I and II, and SMAD Anchor for Receptor Activation in scWAT.
  
  
  CONCLUSIONS
  For the first time, the fact that ROSI inhibits SMAD2 and SMAD3 signaling in a depot-specific manner in diabetic rats was demonstrated. In scWAT, ROSI reduced SMAD2 and SMAD3 phosphorylation, likely through the inhibitory actions of SMAD7 and SMURF2. Induction of proximal components of the SMAD pathway may constitute a feedback mechanism to counteract ROSI-induced lipid synthesis in scWAT.
authors: Department of Human Health & Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors: Marie-Soleil
authors: MS
authors: Beaudoin
authors: Laelie A
authors: LA
authors: Snook
authors: Alicia M
authors: AM
authors: Arkell
authors: Amanda
authors: A
authors: Stefanson
authors: Zhongxiao
authors: Z
authors: Wan
authors: Jeremy A
authors: JA
authors: Simpson
authors: Graham P
authors: GP
authors: Holloway
authors: David C
authors: DC
authors: Wright
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D047495:PPAR gamma / Q000819:agonists*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000502:physiology; D051899:Smad2 Protein / Q000187:drug effects / Q000378:metabolism*; D051900:Smad3 Protein / Q000187:drug effects / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D047495:PPAR gamma; D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D000077154:Rosiglitazone; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat