Docosahexaenoic Acid-Supplementation Prior to Fasting Prevents Muscle Atrophy in Mice

J Cachexia Sarcopenia Muscle. 2016 Dec;7(5):587-603. doi: 10.1002/jcsm.12103. Epub 2016 Feb 15.

Abstract

Background: 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 mass in vivo.

Methods: Six-week-old C57BL/6 mice were fed a DHA-enriched or a control diet for 8 weeks and then fasted for 48 h.

Results: 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.

Conclusions: 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.

Keywords: Akt and AMPK signalling; Autophagy; Lipid droplets; Protein turnover; Ubiquitin–proteasome system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Dietary Supplements*
  • Disease Models, Animal
  • Docosahexaenoic Acids / administration & dosage*
  • Endocannabinoids / metabolism
  • Fasting / metabolism*
  • Fatty Acids / metabolism
  • Gene Expression Regulation / drug effects
  • Glycogen / metabolism
  • Lipid Droplets / metabolism
  • Lipid Metabolism
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Muscular Atrophy / prevention & control
  • Organ Size
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Ubiquitin / metabolism
  • Ubiquitination / drug effects

Substances

  • Endocannabinoids
  • Fatty Acids
  • Ubiquitin
  • Docosahexaenoic Acids
  • Adenosine Triphosphate
  • Glycogen
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Proteasome Endopeptidase Complex