Effects of fenofibrate on lipid parameters in obese rhesus monkeys
Fenofibrate is a member of the fibrate class of hypolipidemic agents used clinically to treat hypertriglyceridemia and mixed hyperlipidemia. The fibrates were developed primarily on the basis of their cholesterol and triglyceride lowering in rodents. Fibrates have historically been ineffective at lo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2001-10-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520322070 |
| _version_ | 1818731762460655616 |
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| author | Deborah A. Winegar Peter J. Brown William O. Wilkison Michael C. Lewis Ronda J. Ott W.Q. Tong H. Roger Brown Jurgen M. Lehmann Steven A. Kliewer Kelli D. Plunket James M. Way Noni L. Bodkin Barbara C. Hansen |
| author_facet | Deborah A. Winegar Peter J. Brown William O. Wilkison Michael C. Lewis Ronda J. Ott W.Q. Tong H. Roger Brown Jurgen M. Lehmann Steven A. Kliewer Kelli D. Plunket James M. Way Noni L. Bodkin Barbara C. Hansen |
| author_sort | Deborah A. Winegar |
| collection | DOAJ |
| description | Fenofibrate is a member of the fibrate class of hypolipidemic agents used clinically to treat hypertriglyceridemia and mixed hyperlipidemia. The fibrates were developed primarily on the basis of their cholesterol and triglyceride lowering in rodents. Fibrates have historically been ineffective at lowering triglycerides in experimentally-induced dyslipidemia in nonhuman primate models. The spontaneously obese rhesus monkey is a well-recognized animal model for the study of human obesity and type 2 diabetes, and many of these monkeys exhibit naturally occurring lipid abnormalities, including elevated triglycerides and low HDL cholesterol (HDL-C), similar to patients with type 2 diabetes. To explore whether the obese rhesus model was predictive of the lipid lowering effects of fibrates, we evaluated fenofibrate in six hypertriglyceridemic, hyperinsulinemic, nondiabetic animals in a 20-week, dose-escalating study. The study consisted of a 4-week baseline period, two treatment periods of 10 mg/kg twice daily (b.i.d) for 4 weeks and 30 mg/kg b.i.d. for 8 weeks, and a 4-week washout period. Fenofibrate (30 mg/kg b.i.d) decreased serum triglycerides 55% and LDL-C 27%, whereas HDL-C increased 35%. Apolipoproteins B-100 and C-III levels were also reduced 70% and 29%, respectively. Food intake, body weight, and plasma glucose were not affected throughout the study. Interestingly, plasma insulin levels decreased 40% during the 30 mg/kg treatment period, suggesting improvement in insulin sensitivity.These results support the use of obese rhesus monkey as an excellent animal model for studying the effects of novel hypolipidemic agents, particularly agents that impact serum triglycerides and HDL-C. |
| first_indexed | 2024-12-17T23:22:50Z |
| format | Article |
| id | doaj.art-e18df182ec9643e695a1b3b91bee8a1d |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T23:22:50Z |
| publishDate | 2001-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-e18df182ec9643e695a1b3b91bee8a1d2022-12-21T21:28:51ZengElsevierJournal of Lipid Research0022-22752001-10-01421015431551Effects of fenofibrate on lipid parameters in obese rhesus monkeysDeborah A. Winegar0Peter J. Brown1William O. Wilkison2Michael C. Lewis3Ronda J. Ott4W.Q. Tong5H. Roger Brown6Jurgen M. Lehmann7Steven A. Kliewer8Kelli D. Plunket9James M. Way10Noni L. Bodkin11Barbara C. Hansen12GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709; To whom correspondence should be addressed. e-mail:GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709Zen-Bio Company, Research Triangle Park, NC 27709; GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709Tularik Inc., San Francisco, CA 94080; GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709Obesity and Diabetes Research Center, University of Maryland School of Medicine, Baltimore, MD 21201Obesity and Diabetes Research Center, University of Maryland School of Medicine, Baltimore, MD 21201Fenofibrate is a member of the fibrate class of hypolipidemic agents used clinically to treat hypertriglyceridemia and mixed hyperlipidemia. The fibrates were developed primarily on the basis of their cholesterol and triglyceride lowering in rodents. Fibrates have historically been ineffective at lowering triglycerides in experimentally-induced dyslipidemia in nonhuman primate models. The spontaneously obese rhesus monkey is a well-recognized animal model for the study of human obesity and type 2 diabetes, and many of these monkeys exhibit naturally occurring lipid abnormalities, including elevated triglycerides and low HDL cholesterol (HDL-C), similar to patients with type 2 diabetes. To explore whether the obese rhesus model was predictive of the lipid lowering effects of fibrates, we evaluated fenofibrate in six hypertriglyceridemic, hyperinsulinemic, nondiabetic animals in a 20-week, dose-escalating study. The study consisted of a 4-week baseline period, two treatment periods of 10 mg/kg twice daily (b.i.d) for 4 weeks and 30 mg/kg b.i.d. for 8 weeks, and a 4-week washout period. Fenofibrate (30 mg/kg b.i.d) decreased serum triglycerides 55% and LDL-C 27%, whereas HDL-C increased 35%. Apolipoproteins B-100 and C-III levels were also reduced 70% and 29%, respectively. Food intake, body weight, and plasma glucose were not affected throughout the study. Interestingly, plasma insulin levels decreased 40% during the 30 mg/kg treatment period, suggesting improvement in insulin sensitivity.These results support the use of obese rhesus monkey as an excellent animal model for studying the effects of novel hypolipidemic agents, particularly agents that impact serum triglycerides and HDL-C.http://www.sciencedirect.com/science/article/pii/S0022227520322070fibratePPARαtriglyceride-loweringHDL-Capolipoprotein C-III |
| spellingShingle | Deborah A. Winegar Peter J. Brown William O. Wilkison Michael C. Lewis Ronda J. Ott W.Q. Tong H. Roger Brown Jurgen M. Lehmann Steven A. Kliewer Kelli D. Plunket James M. Way Noni L. Bodkin Barbara C. Hansen Effects of fenofibrate on lipid parameters in obese rhesus monkeys Journal of Lipid Research fibrate PPARα triglyceride-lowering HDL-C apolipoprotein C-III |
| title | Effects of fenofibrate on lipid parameters in obese rhesus monkeys |
| title_full | Effects of fenofibrate on lipid parameters in obese rhesus monkeys |
| title_fullStr | Effects of fenofibrate on lipid parameters in obese rhesus monkeys |
| title_full_unstemmed | Effects of fenofibrate on lipid parameters in obese rhesus monkeys |
| title_short | Effects of fenofibrate on lipid parameters in obese rhesus monkeys |
| title_sort | effects of fenofibrate on lipid parameters in obese rhesus monkeys |
| topic | fibrate PPARα triglyceride-lowering HDL-C apolipoprotein C-III |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520322070 |
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