Antidiabetic effect of SN158 through PPARα/γ dual activation in ob/ob mice

- SN158 interacts with both PPARα and PPARγ, and increases their transcriptional activities.
- SN158 increases adipogenic differentiation of 3T3-L1 preadipocytes and fatty acid oxidation in hepatocytes.
- SN158 has beneficial effects in the improvement of glucose and lipid metabolism in ob/ob mice.
- SN158 could be developed as an antimetabolic agent to improve glucose/lipid abnormalities and insulin resistance.

In this study, we aimed to demonstrate the antidiabetic potential of (E)-N-(4-(3-(5-bromo-4-hydroxy-2-methoxyphenyl)acryloyl) phenyl)-4-tert-butylbenzamide (SN158) through peroxisome proliferator-activated receptor (PPAR)-α/γ dual activation. SN158 interacted with both PPARα and PPARγ, and increased their transcriptional activities. Simultaneously, SN158 treatment led to an increase in adipogenic differentiation of 3T3-L1 preadipocytes and fatty acid oxidation in hepatocytes. In addition, glucose uptake in myotubes was significantly increased by SN158 treatment. Finally, SN158 significantly lowered the plasma levels of glucose, triglycerides, and free fatty acids in ob/ob mice without severe weight gain and hepatomegaly. These results suggest that SN158 can be useful as a potential therapeutic agent against type 2 diabetes and related metabolic disorders by alleviating glucose and lipid abnormalities.