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

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.

Low-frequency electrical stimulation alleviates immobilization-evoked disuse muscle atrophy by repressing autophagy in skeletal muscle of rabbits

“…Skeletal muscles play an important role in vital body functions such as breathing and movement [ 35 – 37 ]. One study showed that the skeletal muscle weight and CSA were significantly reduced in a model of suspension-induced disuse muscle atrophy [ 38 ]. Our time-point experiment showed the development of disuse atrophy of skeletal muscle during the formation of fixation-induced knee joint contracture in rabbits.…”

Advances in nutritional supplementation for sarcopenia management

“…Skeletal muscle atrophy involves an inflammatory phase that leads to cell death and tissue remodeling and activates endoplasmic reticulum stress (ERS) and autophagy ( 96 , 97 ). Both EPA and DHA potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy by attenuating the increase in PERK and ATG14 expression ( 98 ). In addition, DHA promotes mitochondrial biogenesis and skeletal muscle fiber remodeling ( 99 ) and delays muscle wasting by stimulating intermediate oxidative stress and inhibiting proteasomal degradation of muscle proteins ( 100 ).…”

“…Skeletal muscle atrophy involves an inflammatory phase that leads to cell death and tissue remodeling and activates endoplasmic reticulum stress (ERS) and autophagy (96,97). Both EPA and DHA potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy by attenuating the increase in PERK and ATG14 expression (98).…”

Endoplasmic reticulum stress promotes sepsis‐induced muscle atrophy via activation of STAT3 and Smad3

“…CCAAT enhancer binding protein (C/EBP) homologous protein (CHOP) is a downstream transcription factor, which is activated at multiple levels during ER stress (Marciniak et al, 2004). Skeletal muscle contains an extensive network of ER, recent studies proposed that ER stress and UPR are activated in muscle atrophy caused by diverse factors such as disuse, chronic kidney diseases, and neurodegenerative diseases (Gallot & Bohnert, 2021; Marzuca‐Nassr et al, 2021; Montague et al, 2014; Niida et al, 2020). Jiao et al recently revealed that activation of ER stress is involved in diaphragm contractile dysfunction during sepsis (Jiao et al, 2017).…”