The Peroxisome Proliferator-Activated Receptor (PPAR) α Agonist Fenofibrate Suppresses Chemically Induced Lung Alveolar Proliferative Lesions in Male Obese Hyperlipidemic Mice
Abstract
:1. Introduction
2. Results and Discussion
2.1. Results
2.1.1. General Observation
2.1.2. Incidence and Multiplicity of Pulmonary Proliferative Lesions
2.1.3. Immunohistochemical Expression of IGF-1R, p-Akt, p-Erk1/2, PPARα, and PPARγ in Pulmonary Proliferative Lesions Induced by 4-NQO
2.1.4. Ki-67 Labeling Index of Pulmonary Proliferative Lesions
2.1.5. Serum Triglyceride, Free Fatty Acid, Total Cholesterol, Glucose, Insulin, and Insulin-Like Growth Factor-1 Levels
2.2. Discussion
3. Experimental Section
3.1. Animals, Diet, and Chemicals
3.2. Experimental Design
3.3. Immunohistochemistry
3.4. Plasma IGF-1 and Insulin Levels
3.5. Statistical Analysis
4. Conclusions
Acknowledgments
Conflicts of Interest
- Author ContributionsToshiya Kuno, Kazuya Hata, Yoshinobu Hirose, and Takuji Tanaka designed the study, performed the experiments and drafted the manuscript. Toshiya Kuno and Takuji Tanaka carried out data interpretation. Manabu Takamatsu, Akira Hara, Satoru Takahashi, and Katsumi Imaida provide technical support on experimental design and important comments in improving the manuscript. All authors read and approved the final manuscript.
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Group | Treatment (number of mice examined) | Number of mice with proliferative lung lesions (%) | Number of proliferative lung lesion/mouse | |||
---|---|---|---|---|---|---|
Hyperplasia | Adenoma | Adenocarcinoma | Total | |||
1 | 4-NQO (24) | 8/24 (33) | 0.21 ± 0.41 a | 0.17 ± 0.48 | 0.08 ± 0.28 | 0.46 ± 0.78 |
2 | 4-NQO—0.01% fenofibrate (24) | 4/24 (17) | 0.13 ± 0.45 | 0.08 ± 0.28 | 0 | 0.21 ± 0.51 |
3 | 4-NQO—0.05% fenofibrate (25) | 1/25 (4) b | 0 | 0.04 ± 0.20 | 0 | 0.04 ± 0.20 c |
4 | 0.05% fenofibrate (13) | 1/13 (8) | 0 | 0.08 ± 0.28 | 0 | 0.08 ± 0.28 |
5 | Non-treatment (13) | 1/13 (8) | 0 | 0.08 ± 0.28 | 0 | 0.08 ± 0.28 |
Group | Treatment (number of mice examined) | Triglyceride (mg/dL) | Free fatty acid (mEq/L) | Total cholesterol (mg/dL) | Glucose (mg/dL) | Insulin (ng/dL) | IGF-1 (ng/dL) |
---|---|---|---|---|---|---|---|
1 | 4-NQO (5) | 153.6 ± 43.2 a | 2235.6 ± 542.5 | 266.0 ± 48.2 | 128.4 ± 9.1 | 7.89 ± 2.71 | 547.4 ± 58.4 |
2 | 4-NQO—0.01% fenofibrate (5) | 161.2 ± 17.0 | 1540.8 ± 365.5 b | 250.0 ± 25.0 | 130.2 ± 24.4 | 1.31 ± 0.83 c | 456.3 ± 15.7 c |
3 | 4-NQO—0.05% fenofibrate (5) | 60.8 ± 19.0 c,d | 1154.4 ± 80.0 c | 201.8 ± 27.4 | 131.0 ± 11.7 | 0.16 ± 0.05 c | 367.1 ± 16.0 c |
4 | 0.05% fenofibrate (5) | 119.8 ± 28.0 e | 1218.4 ± 148.1 f | 217.4 ± 48.3 | 109.0 ± 14.7 | 0.05 ± 0.04 e | 317.7 ± 47.8 e |
5 | Non-treatment (5) | 208.2 ± 44.7 | 1876.8 ± 267.7 | 238.0 ± 60.4 | 113.6 ± 16.2 | 10.09 ± 1.07 | 573.8 ± 23.6 |
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Kuno, T.; Hata, K.; Takamatsu, M.; Hara, A.; Hirose, Y.; Takahashi, S.; Imaida, K.; Tanaka, T. The Peroxisome Proliferator-Activated Receptor (PPAR) α Agonist Fenofibrate Suppresses Chemically Induced Lung Alveolar Proliferative Lesions in Male Obese Hyperlipidemic Mice. Int. J. Mol. Sci. 2014, 15, 9160-9172. https://doi.org/10.3390/ijms15059160
Kuno T, Hata K, Takamatsu M, Hara A, Hirose Y, Takahashi S, Imaida K, Tanaka T. The Peroxisome Proliferator-Activated Receptor (PPAR) α Agonist Fenofibrate Suppresses Chemically Induced Lung Alveolar Proliferative Lesions in Male Obese Hyperlipidemic Mice. International Journal of Molecular Sciences. 2014; 15(5):9160-9172. https://doi.org/10.3390/ijms15059160
Chicago/Turabian StyleKuno, Toshiya, Kazuya Hata, Manabu Takamatsu, Akira Hara, Yoshinobu Hirose, Satoru Takahashi, Katsumi Imaida, and Takuji Tanaka. 2014. "The Peroxisome Proliferator-Activated Receptor (PPAR) α Agonist Fenofibrate Suppresses Chemically Induced Lung Alveolar Proliferative Lesions in Male Obese Hyperlipidemic Mice" International Journal of Molecular Sciences 15, no. 5: 9160-9172. https://doi.org/10.3390/ijms15059160