Eicosapentaenoic acid attenuates arthritis-induced muscle wasting acting on atrogin-1 and on myogenic regulatory factors

Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1322-31. doi: 10.1152/ajpregu.00388.2009. Epub 2009 Sep 9.


Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that has anti-inflammatory and anticachectic actions. The aim of this work was to elucidate whether EPA administration is able to prevent an arthritis-induced decrease in body weight and muscle wasting in rats. Arthritis was induced by intradermal injection of Freund's adjuvant; 3 days later, nine rats received 1 g/kg EPA or coconut oil daily. All rats were killed 15 days after adjuvant injection. EPA administration decreased the external signs of arthritis and paw volume as well as liver TNF-alpha mRNA. EPA did not modify arthritis-induced decrease in food intake or body weight gain. However, EPA treatment prevented arthritis-induced increase in muscle TNF-alpha and atrogin-1, whereas it attenuated the decrease in gastrocnemius weight and the increase in MuRF1 mRNA. Arthritis not only decreased myogenic regulatory factors but also increased PCNA, MyoD, and myogenin mRNA in the gastrocnemius. Western blot analysis showed that changes in protein content followed the pattern seen with mRNA. In the control rats, EPA administration increased PCNA and MyoD mRNA and protein. In arthritic rats, EPA did not modify the stimulatory effect of arthritis on these myogenic regulatory factors. The results suggest that in experimental arthritis, in addition to its anti-inflammatory effect, EPA treatment attenuates muscle wasting by decreasing atrogin-1 and MuRF1 gene expression and increasing the transcription factors that regulate myogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / complications*
  • Arthritis, Experimental / metabolism
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Disease Models, Animal
  • Eicosapentaenoic Acid / therapeutic use*
  • Male
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • MyoD Protein / metabolism
  • Myogenic Regulatory Factors / metabolism*
  • Myogenin / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Wistar
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Tripartite Motif Proteins
  • Tumor Necrosis Factor-alpha / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Wasting Syndrome / etiology*
  • Wasting Syndrome / metabolism
  • Wasting Syndrome / prevention & control*


  • Muscle Proteins
  • MyoD Protein
  • Myogenic Regulatory Factors
  • Myogenin
  • Proliferating Cell Nuclear Antigen
  • Tripartite Motif Proteins
  • Tumor Necrosis Factor-alpha
  • Eicosapentaenoic Acid
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases