PPARδ activation protects endothelial function in diabetic mice.

Area of Science:

• Cardiovascular Research
• Metabolic Diseases
• Pharmacology

Background:

• Peroxisome proliferator-activated receptor-δ (PPARδ) agonists show promise for increasing insulin sensitivity in diabetes.
• The role of PPARδ in vascular function, particularly in diabetes, remains unclear.

Purpose of the Study:

• To investigate if PPARδ activation improves endothelial function in diabetic and obese mouse models.
• To elucidate the signaling pathways involved in PPARδ-mediated endothelial protection.

Main Methods:

• Utilized PPARδ knockout and wild-type mice, high-fat diet models, and db/db diabetic mice.
• Assessed endothelium-dependent relaxation (EDR) and flow-mediated dilatation (FMD) using wire and pressure myography.
• Measured nitric oxide (NO) production in primary endothelial cells.

Main Results:

• PPARδ agonist GW1516 restored EDR in high-glucose and db/db mouse aortae ex vivo.
• Oral GW1516 treatment improved aortic EDR and mesenteric artery FMD in obese mice, dependent on PPARδ.
• GW1516's effects on endothelial function involved the PI3K/Akt/eNOS pathway, increasing NO production.

Conclusions:

• PPARδ agonists exert endothelial-protective effects in diabetic mice via the PI3K/Akt/eNOS signaling pathway.
• These findings suggest that PPARδ agonists hold therapeutic potential for managing diabetic vasculopathy.