Korean J Med.
2013 Feb;84(2):238-244.
Effects of FXR Deficiency and Pioglitazone on Atherosclerosis in ApoE-Knockout Mice
- Affiliations
-
- 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. imykh@naver.com
- 2Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
- 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
- 4Preclinical Research Center, Biomedical Research Institute, Seoul National University Bundang Hospital, Seongnam, Korea.
- 5Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea.
- 6Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.
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.
Keyword
MeSH Terms
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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
Apolipoproteins
Blood Glucose
Cholesterol
Lipoproteins
PPAR gamma
Peroxisome Proliferator-Activated Receptors
Receptors, Cytoplasmic and Nuclear
Thiazolidinediones
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