title: Docosahexaenoic acid-supplementation prior to fasting prevents muscle atrophy in mice.
abstract: Muscle wasting prevails in numerous diseases (e.g. diabetes, cardiovascular and kidney diseases, COPD,…) and increases healthcare costs. A major clinical issue is to devise new strategies preventing muscle wasting. We hypothesized that 8-week docosahexaenoic acid (DHA) supplementation prior to fasting may preserve muscle massin vivo.
  
  
  
  Six-week-old C57BL/6 mice were fed a DHA-enriched or a control diet for 8 weeks and then fasted for 48 h.
  
  
  
  Feeding mice a DHA-enriched diet prior to fasting elevated muscle glycogen contents, reduced muscle wasting, blocked the 55% decrease in Akt phosphorylation, and reduced by 30-40% the activation of AMPK, ubiquitination, or autophagy. The DHA-enriched diet fully abolished the fasting induced-messenger RNA (mRNA) over-expression of the endocannabinoid receptor-1. Finally, DHA prevented or modulated the fasting-dependent increase in muscle mRNA levels for Rab18, PLD1, and perilipins, which determine the formation and fate of lipid droplets, in parallel with muscle sparing.
  
  
  
  These data suggest that 8-week DHA supplementation increased energy stores that can be efficiently mobilized, and thus preserved muscle mass in response to fasting through the regulation of Akt- and AMPK-dependent signalling pathways for reducing proteolysis activation. Whether a nutritional strategy aiming at increasing energy status may shorten recovery periods in clinical settings remains to be tested.
authors.affiliation: INRA, UMR 1019 UNH, CRNHF-63000 Auvergne Clermont-Ferrand France; Clermont Université, Université d'Auvergne Unité de Nutrition Humaine BP 10448 F-63000 Clermont-Ferrand France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Deval
authors.affiliation: INRA, UMR 1019 UNH, CRNHF-63000 Auvergne Clermont-Ferrand France; Clermont Université, Université d'Auvergne Unité de Nutrition Humaine BP 10448 F-63000 Clermont-Ferrand France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Capel
authors.affiliation: INRA, UMR 1019 UNH, CRNHF-63000 Auvergne Clermont-Ferrand France; Clermont Université, Université d'Auvergne Unité de Nutrition Humaine BP 10448 F-63000 Clermont-Ferrand France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laillet
authors.affiliation: INRA, UMR 1019 UNH, CRNHF-63000 Auvergne Clermont-Ferrand France; Clermont Université, Université d'Auvergne Unité de Nutrition Humaine BP 10448 F-63000 Clermont-Ferrand France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Polge
authors.affiliation: INRA, UMR 1019 UNH, CRNHF-63000 Auvergne Clermont-Ferrand France; Clermont Université, Université d'Auvergne Unité de Nutrition Humaine BP 10448 F-63000 Clermont-Ferrand France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Béchet
authors.affiliation: INRA, UMR 1019 UNH, CRNHF-63000 Auvergne Clermont-Ferrand France; Clermont Université, Université d'Auvergne Unité de Nutrition Humaine BP 10448 F-63000 Clermont-Ferrand France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Taillandier
authors.affiliation: INRA, UMR 1019 UNH, CRNHF-63000 Auvergne Clermont-Ferrand France; Clermont Université, Université d'Auvergne Unité de Nutrition Humaine BP 10448 F-63000 Clermont-Ferrand France.
authors.forename: Didier
authors.initials: D
authors.lastname: Attaix
authors.affiliation: INRA, UMR 1019 UNH, CRNHF-63000 Auvergne Clermont-Ferrand France; Clermont Université, Université d'Auvergne Unité de Nutrition Humaine BP 10448 F-63000 Clermont-Ferrand France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Combaret
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D063388:Endocannabinoids / Q000378:metabolism; D005215:Fasting / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism; D066292:Lipid Droplets / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009929:Organ Size; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D063388:Endocannabinoids; D005227:Fatty Acids; D025801:Ubiquitin; D004281:Docosahexaenoic Acids; D000255:Adenosine Triphosphate; D006003:Glycogen; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex
keywords: Akt and AMPK signalling; Autophagy; Lipid droplets; Protein turnover; Ubiquitin–proteasome system