Novel effects of rosiglitazone on SMAD2 and SMAD3 signaling in white adipose tissue of diabetic rats. (19th February 2014)

• Record Type: Journal Article
• Authors: Beaudoin, Marie‐Soleil; Snook, Laelie A.; Arkell, Alicia M.; Stefanson, Amanda; Wan, Zhongxiao; Simpson, Jeremy A.; Holloway, Graham P.; Wright, David C.
• Is Part Of: Obesity. Volume 22:Number 7(2014:Jul.)
• Page Start: 1632
• Page End: 1642
• Publication Date: 2014-02-19
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.20717
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby20717-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="oby20717-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="oby20717-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="oby20717-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>