Fatty acids modulate the effect of darglitazone on macrophage CD36 expression

Area of Science:

• Cardiovascular Biology
• Metabolic Disease Research
• Immunology

Background:

• Scavenger receptor-mediated cholesterol uptake by macrophages contributes to atherosclerosis.
• Thiazolidinediones (PPARgamma agonists) treat type II diabetes but may increase CD36, promoting foam cell formation.
• Type II diabetes involves dyslipidemia with high nonesterified fatty acids.

Purpose of the Study:

• To investigate the effect of fatty acids on CD36 expression in human monocytes and macrophages.
• To determine how fatty acids and darglitazone interact to influence CD36 expression.

Main Methods:

• Flow cytometry and RT-PCR were used to assess CD36 mRNA and protein expression.
• High-performance liquid chromatography analyzed cellular lipid content.
• Human monocytes and macrophages were utilized.

Main Results:

• Darglitazone alone increased CD36 mRNA and protein in macrophages and triglyceride accumulation.
• In the presence of albumin-bound fatty acids, darglitazone did not increase CD36 expression or triglyceride levels.
• Fatty acids alone upregulated CD36 mRNA and protein expression.

Conclusions:

• Fatty acids play a role in regulating macrophage CD36 expression and foam cell formation.
• The proatherogenic effect of thiazolidinediones on CD36 may be mitigated by physiological levels of albumin-bound fatty acids.