Gemfibrozil not fenofibrate decreases systemic glucose level via PPARα

Area of Science:

• Pharmacology
• Metabolic Diseases
• Molecular Biology

Background:

• Dyslipidemia and diabetes pose significant clinical challenges.
• The role of fibrates in treating dyslipidemia with metabolic syndrome is not well-established.

Purpose of the Study:

• To investigate the effects of gemfibrozil and fenofibrate on glucose metabolism.
• To determine the role of Peroxisome proliferator-activated receptor alpha (PPARα) in mediating these effects.

Main Methods:

• Wild-type and PPARα-null mice were treated with gemfibrozil and fenofibrate.
• Assessed blood glucose, liver glycogen, and gene expression related to glucose metabolism.
• Quantitative polymerase chain reaction (qPCR) was used to analyze gene expression.

Main Results:

• Gemfibrozil, but not fenofibrate, dose-dependently reduced blood glucose and liver glycogen in wild-type mice.
• These effects were absent in PPARα-null mice, indicating PPARα dependence.
• Gemfibrozil modulated the transcription of key glucose metabolism genes, pyruvate kinase and gluconolactonase, in a PPARα-dependent manner.

Conclusions:

• Gemfibrozil, via PPARα activation, effectively lowers systemic glucose and liver glycogen.
• Fenofibrate did not show similar glucose-lowering effects in this model.
• Gemfibrozil shows potential for managing dyslipidemia in patients with concurrent diabetes or hyperglycemia.