Endoplasmic Reticulum Stress and Autophagy Markers in Soleus Muscle Disuse-Induced Atrophy of Rats Treated with Fish Oil

Nutrients. 2021 Jul 3;13(7):2298. doi: 10.3390/nu13072298.

Abstract

Endoplasmic reticulum stress (ERS) and autophagy pathways are implicated in disuse muscle atrophy. The effects of high eicosapentaenoic (EPA) or high docosahexaenoic (DHA) fish oils on soleus muscle ERS and autophagy markers were investigated in a rat hindlimb suspension (HS) atrophy model. Adult Wistar male rats received daily by gavage supplementation (0.3 mL per 100 g b.w.) of mineral oil or high EPA or high DHA fish oils (FOs) for two weeks. Afterward, the rats were subjected to HS and the respective treatments concomitantly for an additional two-week period. After four weeks, we evaluated ERS and autophagy markers in the soleus muscle. Results were analyzed using two-way analysis of variance (ANOVA) and Bonferroni post hoc test. Gastrocnemius muscle ω-6/ω-3 fatty acids (FAs) ratio was decreased by both FOs indicating the tissue incorporation of omega-3 fatty acids. HS altered (p < 0.05) the protein content (decreasing total p38 and BiP and increasing p-JNK2/total JNK2 ratio, and caspase 3) and gene expressions (decreasing BiP and increasing IRE1 and PERK) of ERS and autophagy (decreasing Beclin and increasing LC3 and ATG14) markers in soleus. Both FOs attenuated (p < 0.05) the increase in PERK and ATG14 expressions induced by HS. Thus, both FOs could potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy.

Keywords: docosahexaenoic acid; eicosapentanoic acid; hindlimb suspension; skeletal muscle atrophy; unfolded protein response; ω-3 fatty acids.

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Docosahexaenoic Acids / pharmacology
  • Eicosapentaenoic Acid / pharmacology
  • Endoplasmic Reticulum Stress / drug effects*
  • Fish Oils / pharmacology*
  • Hindlimb Suspension
  • Male
  • Muscle, Skeletal / metabolism*
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / therapy*
  • Rats
  • Rats, Wistar

Substances

  • Biomarkers
  • Fish Oils
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid