Fenofibrate reduces postprandial hypertriglyceridemia in CD36 knockout mice.

Abstract

AIM:

Metabolic syndrome (MetS) and postprandial hypertriglyceridemia (PHTG) are closely related and both are associated with coronary heart disease. We have demonstrated that CD36 deficiency is prevalent in the genetic background of MetS and is accompanied by PHTG concomitantly with an increase in remnants and a decrease in high density lipoprotein cholesterol. These findings make CD36 knockout mice (CD36KO) an interesting model for evaluating PHTG in MetS. Fenofibrate was reported to reduce fasting and postprandial triglyceride (TG) levels in hypertriglyceridemic subjects with MetS. To define its mechanism, we investigated the effect of fenofibrate on PHTG in CD36KO.

METHODS:

Wild-type (WT) and CD36KO mice were fed chow diet and fenofibrate for two weeks. TG concentrations and lipoprotein profiles were assessed during fasting and in the postprandial state in plasma; intestinal mucosa and lymph were collected after oral fat loading for both treatment groups.

RESULTS:

Fenofibrate treatment markedly suppressed the postprandial TG response in CD36KO along with decreased apoB-48 levels in plasma. HPLC analysis depicted the decrease of TG content in chylomicrons (CM) and CM remnant-sized lipoproteins contributed to this suppression, suggesting that CM and CM remnant production in the intestines might be attenuated by fenofibrate. ApoB-48 and TG levels in intestinal lymph were markedly reduced after treatment. Intestinal mRNA expression of apoB was also reduced in the postprandial state after fenofibrate administration without affecting any other genes related to CM assembly and production.

CONCLUSION:

Fenofibrate reduces PHTG in CD36KO partially through attenuating intestinal CM production.

• Authors: José C Sandoval, Yumiko Nakagawa-Toyama, Daisaku Masuda, Yoshihiro Tochino, Hajime Nakaoka, Ryota Kawase, Miyako Yuasa-Kawase, Kazuhiro Nakatani, Miwako Inagaki, Kazumi Tsubakio-Yamamoto, Tohru Ohama, Makoto Nishida, Masato Ishigami, Issei Komuro, Shizuya Yamashita
• Journal: Journal of atherosclerosis and thrombosis (J Atheroscler Thromb) Vol. 17 Issue 6 Pg. 610-8 (Jun 30 2010) ISSN: 1880-3873 [Electronic] Japan
• PMID: 20351468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD36 Antigens
• Chylomicrons
• Fenofibrate

Topics

• Animals
• CD36 Antigens (deficiency)
• Chylomicrons (biosynthesis)
• Fenofibrate (pharmacology)
• Hypertriglyceridemia (drug therapy, prevention & control)
• Intestinal Mucosa (metabolism)
• Metabolic Syndrome
• Mice
• Mice, Knockout
• Postprandial Period