Document Detail

Fenofibrate, a PPAR{alpha} agonist, decreases atrogenes and myostatin expression and improves arthritis-induced skeletal muscle atrophy.
MedLine Citation:
PMID:  21304067     Owner:  NLM     Status:  MEDLINE    
Arthritis is a chronic inflammatory illness that induces cachexia, which has a direct impact on morbidity and mortality. Fenofibrate, a selective PPARα activator prescribed to treat human dyslipidemia, has been reported to decrease inflammation in rheumatoid arthritis patients. The aim of this study was to elucidate whether fenofibrate is able to ameliorate skeletal muscle wasting in adjuvant-induced arthritis, an experimental model of rheumatoid arthritis. On day 4 after adjuvant injection, control and arthritic rats were treated with 300 mg/kg fenofibrate until day 15, when all rats were euthanized. Fenofibrate decreased external signs of arthritis and liver TNFα and blocked arthritis-induced decreased in PPARα expression in the gastrocnemius muscle. Arthritis decreased gastrocnemius weight, which results from a decrease in cross-section area and myofiber size, whereas fenofibrate administration to arthritic rats attenuated the decrease in both gastrocnemius weight and fast myofiber size. Fenofibrate treatment prevented arthritis-induced increase in atrogin-1 and MuRF1 expression in the gastrocnemius. Neither arthritis nor fenofibrate administration modify Akt-FoxO3 signaling. Myostatin expression was not modified by arthritis, but fenofibrate decreased myostatin expression in the gastrocnemius of arthritic rats. Arthritis increased muscle expression of MyoD, PCNA, and myogenin in the rats treated with vehicle but not in those treated with fenofibrate. The results indicate that, in experimental arthritis, fenofibrate decreases skeletal muscle atrophy through inhibition of the ubiquitin-proteasome system and myostatin.
Estíbaliz Castillero; María Paz Nieto-Bona; Carmen Fernández-Galaz; Ana Isabel Martín; María López-Menduiña; Miriam Granado; María Angeles Villanúa; Asunción López-Calderón
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-02-08
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  300     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-27     Completed Date:  2011-06-28     Revised Date:  2012-03-06    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E790-9     Citation Subset:  IM    
Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, Madrid, Spain 28040.
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MeSH Terms
Arthritis, Experimental / drug therapy,  pathology*
Body Weight / drug effects
Eating / drug effects
Fenofibrate / pharmacology*
Gene Expression / drug effects
Hypolipidemic Agents / pharmacology*
Lipids / blood
Muscle Fibers, Skeletal / drug effects,  ultrastructure
Muscle Proteins / biosynthesis*,  genetics
Muscle, Skeletal / pathology*
Myogenic Regulatory Factors / biosynthesis,  genetics
Myostatin / biosynthesis*,  genetics*
Organ Size / drug effects
PPAR gamma / agonists*
Rats, Wistar
SKP Cullin F-Box Protein Ligases / biosynthesis*,  genetics
Ubiquitin-Protein Ligases / biosynthesis*,  genetics
Reg. No./Substance:
0/Hypolipidemic Agents; 0/Lipids; 0/Muscle Proteins; 0/Myogenic Regulatory Factors; 0/Myostatin; 0/PPAR gamma; 49562-28-9/Fenofibrate; EC protein, rat; EC Cullin F-Box Protein Ligases; EC protein, rat; EC Ligases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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