PPAR-β/δ activation promotes phospholipid transfer protein expression

Area of Science:

• Lipid metabolism
• Molecular biology
• Pharmacology

Background:

• Peroxisome proliferator-activated receptor (PPAR)-β/δ is a potential therapeutic target for dyslipidemia.
• PPAR-β/δ activation shows promise for improving HDL cholesterol (HDL-C).

Purpose of the Study:

• To investigate the effects of the PPAR-β/δ agonist GW0742 on HDL composition and liver HDL-related gene expression.
• To determine the role of PPAR-β/δ in mediating these effects.

Main Methods:

• Experiments were conducted in C57BL/6 wild-type, LDLR-deficient, and PPAR-β/δ-deficient mice treated with GW0742 or vehicle.
• GW0742 treatment involved a dosage of 10mg/kg/day for 14 days.
• PLTP mRNA expression was assessed in mouse macrophages (J774) and human cells (THP-1, Huh7).

Main Results:

• GW0742 upregulated liver phospholipid transfer protein (Pltp) gene expression and increased serum PLTP activity in mice.
• In wild-type mice, GW0742 significantly increased serum HDL-C and HDL phospholipids, enhancing preβ-HDL formation.
• The effects of GW0742 on Pltp expression and PLTP activity were abolished in PPAR-β/δ-deficient mice, confirming PPAR-β/δ dependency.
• GW0742 stimulated PLTP mRNA expression in various macrophage and hepatoma cell lines.

Conclusions:

• GW0742-activated PPAR-β/δ transcriptionally upregulates Pltp expression in liver and cultured cells, leading to increased serum PLTP activity.
• PPAR-β/δ activation modulates PLTP-mediated preβ-HDL formation and macrophage cholesterol efflux.