WSF-7 Inhibits Obesity-Mediated PPARγ Phosphorylation and Improves Insulin Sensitivity in 3T3-L1 Adipocytes.

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ), the molecular target for antidiabetic thiazolidinediones (TZDs), is a master regulator of preadipocyte differentiation and lipid metabolism. The adverse side effects of TZDs, arising from their potent agonistic activity, can be minimized by PPARγ partial agonists or PPARγ non-agonists without loss of insulin sensitization. In this study, we reported that WSF-7, a synthetic chemical derived from natural monoterpene α-pinene, is a partial PPARγ agonist. We found that WSF-7 binds directly to PPARγ. Activation of PPARγ by WSF-7 promotes adipogenesis, adiponectin oligomerization and insulin-induced glucose uptake. WSF-7 also inhibits obesity-mediated PPARγ phosphorylation at serine (Ser)273 and improves insulin sensitivity of 3T3-L1 adipocytes. Our study suggested that WSF-7 activates PPARγ transcription by a mechanism different from that of rosiglitazone or luteolin. Therefore, WSF-7 might be a potential therapeutic drug to treat type 2 diabetes.

• Authors: Yudian Zhang, Yunyun Wang, Xiaochuan Li, Kerui Gu, Mingxin Li, Yan Zhang, Zhijie Zhang, Shifa Wang, Zhen Li
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 43 Issue 3 Pg. 526-532 ( 2020) ISSN: 1347-5215 [Electronic] Japan
• PMID: 32115511 (Publication Type: Journal Article)

Chemical References

• Adiponectin
• Insulin
• Monoterpenes
• PPAR gamma
• Glucose

Topics

• 3T3-L1 Cells
• Adipocytes (drug effects)
• Adiponectin (metabolism)
• Animals
• Glucose (metabolism)
• Insulin (metabolism)
• Mice
• Monoterpenes (chemistry, pharmacology)
• Obesity (metabolism)
• PPAR gamma (agonists, metabolism)
• Phosphorylation (drug effects)