n-3 Fatty acids preserve muscle mass and insulin sensitivity in a rat model of energy restriction.
In obese subjects, the loss of fat mass during energy restriction is often accompanied by a loss of muscle mass. The hypothesis that n-3 PUFA, which modulate protein homoeostasis via effects on insulin sensitivity, could contribute to maintain muscle mass during energy restriction was tested in rats fed a high-fat diet (4 weeks) rich in 18 : 1 n-9 (oleic acid, OLE-R), 18 : 3 n-3 (α-linolenic acid, ALA-R) or n-3 long-chain (LC-R) fatty acid and then energy restricted (8 weeks). A control group (OLE-ad libitum (AL)) was maintained with AL diet throughout the study. Rats were killed 10 min after an i.v. insulin injection. All energy-restricted rats lost weight and fat mass, but only the OLE-R group showed a significant muscle loss. The Gastrocnemius muscle was enriched with ALA in the ALA-R group and with LC-PUFA in the ALA-R and LC-R groups. The proteolytic ubiquitin-proteasome system was differentially affected by energy restriction, with MAFbx and muscle ring finger-1 mRNA levels being decreased in the LC-R group (-30 and -20 %, respectively). RAC-α serine/threonine-protein kinase and insulin receptor substrate 1 phosphorylation levels increased in the LC-R group (+70 %), together with insulin receptor mRNA (+50 %). The ALA-R group showed the same overall activation pattern as the LC-R group, although to a lesser extent. In conclusion, dietary n-3 PUFA prevent the loss of muscle mass associated with energy restriction, probably by an improvement in the insulin-signalling pathway activation, in relation to enrichment of plasma membranes in n-3 LC-PUFA.
1UMR Physiologie de la Nutrition et du Comportement Alimentaire,AgroParisTech,INRA,Université Paris-Saclay,75005 Paris,France.
Guillaume
G
Galmiche
1UMR Physiologie de la Nutrition et du Comportement Alimentaire,AgroParisTech,INRA,Université Paris-Saclay,75005 Paris,France.
Jean-François
JF
Huneau
1UMR Physiologie de la Nutrition et du Comportement Alimentaire,AgroParisTech,INRA,Université Paris-Saclay,75005 Paris,France.
Véronique
V
Mathé
2UMR PEGASE,Agrocampus Ouest,INRA,35590 Saint-Gilles,France.
Jacques
J
Mourot
3Terres Univia,11 rue de Monceau,CS 60003,75008 Paris,France.
Noémie
N
Simon
3Terres Univia,11 rue de Monceau,CS 60003,75008 Paris,France.
Céline
C
Le Guillou
1UMR Physiologie de la Nutrition et du Comportement Alimentaire,AgroParisTech,INRA,Université Paris-Saclay,75005 Paris,France.
Dominique
D
Hermier
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001823:Body Composition; D031204:Caloric Restriction; D004032:Diet; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage; D005227:Fatty Acids / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000032:analysis; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D019301:Oleic Acid / Q000008:administration & dosage; D010743:Phospholipids / Q000737:chemistry; D059748:Proteolysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000235:genetics; D015398:Signal Transduction; D017962:alpha-Linolenic Acid / Q000008:administration & dosage / Q000032:analysis
D015415:Biomarkers; D004041:Dietary Fats; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D007328:Insulin; D008055:Lipids; D009124:Muscle Proteins; D010743:Phospholipids; D012333:RNA, Messenger; D017962:alpha-Linolenic Acid; D019301:Oleic Acid; D011972:Receptor, Insulin

               n-3 Fatty acids;  AKT RAC-α serine/threonine-protein kinase;  AL 
                  ad libitum
               ;  ALA 
                  α-linolenic acid;  FA fatty acid;  Fbxo32 F-box protein 32;  HFI high-fat induction;  HOMA homeostasis model assessment on insulin resistance;  IRS-1 insulin receptor substrate-1;  LA linoleic acid;  LC 
                  n-3 long-chain;  MetSynd metabolic syndrome;  MuRF1 muscle ring finger 1;  OLE oleic acid;  R restricted;  S6RP ribosomal protein S6;  mTOR mammalian target of rapamycin; Insulin signalling; Protein homoeostasis; Weight loss