Edorium Journal of

Biochemistry

 
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Review Article
 
Fibrates: From PPARα activation to clinical use in the metabolic syndrome
Kate Elizabeth Shipman1, Richard C. Strange2, Sudarshan Ramachandran3,4,5
1MRCP, FRCPath, Specialist Registrar in Chemical Pathology, Department of Clinical Biochemistry, University Hospital Birmingham, Birmingham, West Midlands, United Kingdom.
2PhD, FRCPath, Professor of Clinical Biochemistry, Institute for Science and Technology in Medicine, Keele University Medical School, Keele University, Staffordshire, UK, ST5 5BG.
3PhD, FRCPath, Consultant Chemical Pathologist, Department of Clinical Biochemistry, Heart of England NHS Foundation Trust, Birmingham, West Midlands, United Kingdom.
4Professor of Metabolic Medicine, Department of Clinical Biochemistry, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, Staffordshire ST4 6QG.
5Professor (Hon) of Metabolic Medicine, Faculty of Health Sciences, Staffordshire University, College Road, Stoke on Trent, Staffordshire ST4 2DE.

Article ID: 100003B01KS2015
doi:10.5348/B01-2015-3-RA-3

Address correspondence to:
Professor Sudarshan Ramachandran
Department of Clinical Biochemistry, Heart of England NHS Foundation Trust
Good Hope Hospital, Rectory Road
Sutton Coldfield, West Midlands, B75 7RR
United Kingdom

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How to cite this article
Shipman KE, Strange RC, Ramachandran S. Fibrates: From PPARα activation to clinical use in the metabolic syndrome. Edorium J Biochem 2015;1:8–18.


Abstract
Pharmaceutical interest in fibric acid derivatives followed the observation in 1953 that administration to rats and humans of compounds derived from dehydrocholic acid resulted in reductions in serum cholesterol levels. It was subsequently shown that these compounds, collectively termed fibrates, effect changes in nuclear transcription leading to a lowering in serum, of triglycerides and low, density lipoprotein cholesterol and elevation of high density lipoprotein cholesterol. However, despite this initial promise large randomized control trials of different fibrates using various primary outcomes have produced discrepant results though sub-group analysis and meta-analysis, do suggest improved benefit in those with atherogenic dyslipidemia. In particular, gemfibrozil trials have shown significant benefit in primary outcomes with other fibrates showing benefit in those with decreased high density lipoprotein cholesterol and raised triglycerides and in secondary outcomes such as diabetic retinopathy. We now after a description of their, actions, review the evidence for fibrate use with a focus on the metabolic syndrome and recommend that their clinical use is targeted at those with reduced high density lipoprotein cholesterol levels and hypertriglyceridemia.

Keywords: Cardiovascular disease risk, Fibrate, High density lipoprotein cholesterol (HDL-C), Metabolic syndrome, Triglycerides


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Author Contributions
Kate Elizabeth Shipman – Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Richard C Strange – Analysis and interpretation of data, Revising it critically for important intellectual content, Final approval of the version to be published
Sudarshan Ramachandran – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Guarantor of submission
The corresponding author is the guarantor of submission.
Source of support
None
Conflict of interest
Authors declare no conflict of interest.
Copyright
© 2015 Kate Elizabeth Shipman et al. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.



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