Fenofibrate reduces postprandial hypertriglyceridemia in CD36 knockout mice.
OBJECTIVE
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.


CONCLUSIONS
Fenofibrate reduces PHTG in CD36KO partially through attenuating intestinal CM production.
Sandoval
José C
JC
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Nakagawa-Toyama
Yumiko
Y
Masuda
Daisaku
D
Tochino
Yoshihiro
Y
Nakaoka
Hajime
H
Kawase
Ryota
R
Yuasa-Kawase
Miyako
M
Nakatani
Kazuhiro
K
Inagaki
Miwako
M
Tsubakio-Yamamoto
Kazumi
K
Ohama
Tohru
T
Nishida
Makoto
M
Ishigami
Masato
M
Komuro
Issei
I
Yamashita
Shizuya
S
D000818:Animals; D018955:CD36 Antigens / Q000172:deficiency*; D002914:Chylomicrons / Q000096:biosynthesis; D011345:Fenofibrate / Q000494:pharmacology*; D015228:Hypertriglyceridemia / Q000188:drug therapy* / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000378:metabolism; D024821:Metabolic Syndrome; D051379:Mice; D018345:Mice, Knockout; D019518:Postprandial Period
D018955:CD36 Antigens; D002914:Chylomicrons; D011345:Fenofibrate