%0 Journal Article
%T Pseudoginsenoside F11, a Novel Partial PPAR¦Ã Agonist, Promotes Adiponectin Oligomerization and Secretion in 3T3-L1 Adipocytes
%A Guoyu Wu
%A Junyang Yi
%A Ling Liu
%A Pengcheng Wang
%A Zhijie Zhang
%A Zhen Li
%J PPAR Research
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/701017
%X PPAR¦Ã is a nuclear hormone receptor that functions as a master regulator of adipocyte differentiation and development. Full PPAR¦Ã agonists, such as the thiazolidinediones (TZDs), have been widely used to treat type 2 diabetes. However, they are characterized by undesirable side effects due to their strong agonist activities. Pseudoginsenoside F11 (p-F11) is an ocotillol-type ginsenoside isolated from Panax quinquefolium L. (American ginseng). In this study, we found that p-F11 activates PPAR¦Ã with modest adipogenic activity. In addition, p-F11 promotes adiponectin oligomerization and secretion in 3T3-L1 adipocytes. We also found that p-F11 inhibits obesity-linked phosphorylation of PPAR¦Ã at Ser-273 by Cdk5. Therefore, p-F11 is a novel partial PPAR¦Ã agonist, which might have the potential to be developed as a new PPAR¦Ã-targeted therapeutics for type 2 diabetes. 1. Introduction The nuclear hormone receptor PPAR¦Ã (peroxisome proliferator-activated receptor ¦Ã) is a ligand-activated transcription factor highly expressed in the adipose tissues [1]. By binding to PPAR¦Ã-responsive regulatory elements as heterodimers with retinoid X receptor (RXR), PPAR¦Ã regulates the expression of networks of genes involved in adipogenesis, lipid metabolism, inflammation, and maintenance of metabolic homeostasis [2]. PPAR¦Ã consists of an amino terminal activation domain (AF-1), a highly conserved DNA-binding domain (DBD), and a C-terminal ligand-binding domain (LBD) containing a ligand-dependent transactivation domain (AF-2) [3]. Ligand binding promotes a conformational change which allows for differential recruitment of cofactors and subsequent modulation of PPAR¦Ã activity [4, 5]. PPAR¦Ã is the pharmacological target of the insulin-sensitizing thiazolidinediones (TZDs) that have been widely used in the treatment of type 2 diabetes. TZDs function as selective PPAR¦Ã ligands and induce transcription of PPAR¦Ã-targeted genes [6]. Derivatives of TZD, such as rosiglitazone (Avandia) and pioglitazone (Actos), are highly effective in treating type 2 diabetes and are well tolerated by the majority of patients [1]. However, they are associated with various undesirable side effects, including weight gain, fluid retention, edema, congestive heart failure, and bone fracture [7, 8]. Long-term use of TZDs may be associated with increased risk of bladder cancer [9]. These limitations have raised substantial concerns and significantly impaired their future in many countries [10]. Therefore, it is critical to develop TZD substitutes for improved therapies of type 2 diabetes. Studies in animal
%U http://www.hindawi.com/journals/ppar/2013/701017/