title: Impact of fasting on the rhythmic expression of myogenic and metabolic factors in skeletal muscle of adult mice.
abstract: Circadian rhythms and metabolism are tightly integrated, and rhythmic expression of metabolic factors is common in homeostatic processes. We measured the temporal changes in the expression of myogenic regulatory factors and expression and activity level of molecules involved in protein metabolism in skeletal muscles and livers in mice and examined the impact of fasting. Tissues were collected over 24 h (at zeitgeber times ZT1, ZT5, ZT9, ZT13, ZT17, ZT21, and ZT1 the following day) from adult male C57Bl/6J mice that had been either freely fed or fasted for 24 h. In skeletal muscle, there was a robust rise in the mRNA expression of the myogenic regulatory factors MyoD and myogenin during dark hours which was strongly suppressed by fasting. Circadian pattern was observed for mRNA of MuRF1, Akt1, and ribosomal protein S6 in muscles in fed and fasted mice and for Fbxo32 in fed mice. Activity (phosphorylation) levels of Akt(Ser473) displayed temporal regulation in fasted (but not fed) mice and were high at ZT9. Fasting caused significant reductions in phosphorylation for both Akt and S6 in muscles, indicative of inactivation. Hepatic phosphorylated Akt(Ser473) and S6(Ser235/236) proteins did not exhibit daily rhythms. Fasting significantly reduced hepatic Akt(473) phosphorylation compared with fed levels, although (unlike in muscle) it did not affect S6(Ser235/236) phosphorylation. This in vivo circadian study addresses for the first time the signaling activities of key molecules related to protein turnover and their possible cross-regulation of expression of genes related to protein degradation.
authors.affiliation: School of Anatomy, Physiology and Human Biology, the University of Western Australia, Crawley, Western Australia, Australia. tea.shavlakadze@uwa.edu.au
authors.forename: T
authors.initials: T
authors.lastname: Shavlakadze
authors.forename: T
authors.initials: T
authors.lastname: Anwari
authors.forename: Z
authors.initials: Z
authors.lastname: Soffe
authors.forename: G
authors.initials: G
authors.lastname: Cozens
authors.forename: P J
authors.initials: PJ
authors.lastname: Mark
authors.forename: C
authors.initials: C
authors.lastname: Gondro
authors.forename: M D
authors.initials: MD
authors.lastname: Grounds
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D003624:Darkness; D005508:Food Deprivation; D005766:Gastrointestinal Contents / Q000737:chemistry; D005786:Gene Expression Regulation / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038601:Ribosomal Protein S6 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018008:Myogenin; D012333:RNA, Messenger; D038601:Ribosomal Protein S6; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D003345:Corticosterone
keywords: Akt; Fbxo32; MuRF1; MyoD; circadian rhythm