Fenofibrate reduces postprandial hypertriglyceridemia in CD36 knockout mice.

Area of Science:

• Lipid metabolism
• Cardiovascular disease research
• Pharmacology

Background:

• Metabolic syndrome (MetS) and postprandial hypertriglyceridemia (PHTG) are linked to coronary heart disease.
• CD36 deficiency is associated with MetS, PHTG, increased remnants, and decreased HDL cholesterol.
• CD36 knockout (CD36KO) mice serve as a model for studying PHTG in MetS.

Purpose of the Study:

• To investigate the mechanism by which fenofibrate reduces PHTG in CD36KO mice.
• To evaluate the effect of fenofibrate on postprandial triglyceride levels and lipoprotein profiles in a genetic model of MetS.

Main Methods:

• Wild-type (WT) and CD36KO mice were treated with fenofibrate or a control diet for two weeks.
• Plasma triglyceride (TG) and lipoprotein profiles were analyzed in fasting and postprandial states.
• Intestinal lymph and mucosa were collected after oral fat loading to assess chylomicron (CM) production and related gene expression.

Main Results:

• Fenofibrate significantly suppressed postprandial TG response and reduced apoB-48 levels in CD36KO mice.
• HPLC analysis showed decreased TG content in chylomicrons and CM remnants, indicating attenuated intestinal CM production.
• ApoB-48 and TG levels in intestinal lymph were reduced, along with decreased intestinal apoB mRNA expression post-fenofibrate treatment.

Conclusions:

• Fenofibrate ameliorates PHTG in CD36KO mice.
• The mechanism involves the attenuation of intestinal chylomicron production, partially explaining fenofibrate's efficacy in MetS-related hypertriglyceridemia.