Effects of FXR Deficiency and Pioglitazone on Atherosclerosis in ApoE-Knockout Mice.
- Author:
Young Joo PARK
1
;
Min Joo KIM
;
Kwan Jae LEE
;
Ji Yeon HWANG
;
Yenna LEE
;
Hwa Young AHN
;
Sung Hee CHOI
;
Min Kyong MOON
;
Soo LIM
;
Hak C JANG
;
Ka Hee YI
Author Information
1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. imykh@naver.com
- Publication Type:Original Article
- Keywords:
Farnesoid X-activated receptor;
Peroxisome proliferator-activated receptors;
Pioglitazone;
Atherosclerosis
- MeSH:
Animals;
Aorta;
Apolipoproteins;
Atherosclerosis;
Blood Glucose;
Body Weight;
Cholesterol;
Diet;
Lipid Metabolism;
Lipoproteins;
Liver;
Mice;
Peroxisome Proliferator-Activated Receptors;
Peroxisomes;
Plaque, Atherosclerotic;
PPAR gamma;
Receptors, Cytoplasmic and Nuclear;
Thiazolidinediones
- From:Korean Journal of Medicine
2013;84(2):238-244
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND/AIMS: Both the farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) play important roles in lipid metabolism and atherosclerosis. We investigated the interaction between FXR and PPARgamma. METHODS: Apolipoprotein E knockout (ApoE-/-) mice and FXR knockout (FXR-/-) mice were crossed to generate ApoE-/-FXR-/- mice. The mice were divided into ApoE-/-, ApoE-/-FXR-/-, and ApoE-/-FXR-/- + pioglitazone groups. All mice were fed a high-fat, high-cholesterol diet for 12 weeks. The ApoE-/-FXR-/- + pioglitazone group was also treated with pioglitazone, 20 mg/kg body weight. Body weight, blood glucose level, lipid profile, and liver enzyme levels were measured. To evaluate atherosclerotic lesions, the aorta was stained with Oil red O. RESULTS: There were no differences in body weight or blood glucose level among the three groups. The serum lipid concentration and liver enzyme levels increased in the ApoE-/-FXR-/- group compared with the ApoE-/- group (p < 0.01). The ApoE-/-FXR-/- + pioglitazone group had lower high-density lipoprotein (HDL) (55 +/- 4 vs. 28 +/- 2 mg/dL, p < 0.01) and low-density lipoprotein (LDL) (797 +/- 26 vs. 682 +/- 47 mg/dL, p = 0.04) cholesterol than the ApoE-/-FXR-/- group. The respective percentages of aortic atherosclerotic plaques in the ApoE-/-, ApoE-/-FXR-/-, and ApoE-/-FXR-/- + pioglitazone groups were 2.7 +/- 0.2%, 7.7 +/- 1.2%, and 18.6 +/- 1.0%. In ApoE-/-FXR-/- mice, the administration of pioglitazone significantly increased the number of atherosclerotic lesions (p = 0.02). CONCLUSIONS: Pioglitazone increased the number of atherosclerotic plaques in ApoE-/-FXR-/- mice. This suggests that when FXR is inhibited, the activation of PPARgamma can aggravate atherosclerosis.
