Dietary fish oil alleviates soleus atrophy during immobilization in association with Akt signaling to p70s6k and E3 ubiquitin ligases in rats.
Reduced muscle activity leads to impaired insulin signaling, which leads to loss of contractile proteins and muscle mass via the Akt pathway. Dietary fish oil rich in long chain n-3 polyunsaturated fatty acids has been shown to prevent insulin signaling resistance in skeletal muscle. This study was conducted to elucidate the protective effect of dietary fish oil on disuse-induced perturbations in insulin signaling and soleus muscle atrophy. To accomplish this, rats were fed a corn-oil- (control) or fish-oil-based diet for 2 weeks, and then subjected to hindlimb immobilization while still receiving the same diets. After 10 days of immobilization, the soleus muscle mass and myosin heavy chain level had markedly decreased; however, these losses were significantly suppressed in rats fed dietary fish oil, compared with the control group. Dietary fish oil nearly completely attenuated the disturbances in activation of the Akt and p70 S6 kinase proteins, as well as the gene expression of muscle-specific E3 ubiquitin ligases (muscle atrophy F-box and muscle RING finger 1). However, insulin receptor substrate 1 associated with the p85 subunit of phosphoinositide 3-kinase was not altered during immobilization. Dietary fish oil also inhibited alterations in the gene expression of cyclooxygenase-2 and inducible nitric oxide synthase, with no additional observation of oxidative stress. Collectively, these findings indicate that dietary fish oil prior to and during immobilization may alleviate the immobilization-induced soleus muscle atrophy, at least in part, via the Akt pathway through E3 ubiquitin ligases and p70s6k.
You
Jae-Sung
JS
Department of Food and Nutrition, Seoul National University, Seoul 151-742, Korea.
Park
Mi-Na
MN
Song
Wook
W
Lee
Yeon-Sook
YS
D000818:Animals; D003314:Corn Oil / Q000008:administration & dosage; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005395:Fish Oils / Q000008:administration & dosage*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019417:Hindlimb Suspension; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D005395:Fish Oils; D018836:Inflammation Mediators; D007328:Insulin; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D003314:Corn Oil; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D018995:Myosin Heavy Chains