title: SREBP-1 transcription factors regulate skeletal muscle cell size by controlling protein synthesis through myogenic regulatory factors.
abstract: SREBP-1 are ubiquitously expressed transcription factors, strongly expressed in lipogenic tissues where they regulate several metabolic processes like fatty acid synthesis. In skeletal muscle, SREBP-1 proteins regulate the expression of hundreds of genes, and we previously showed that their overexpression induced muscle atrophy together with a combined lack of expression of myogenic regulatory factors. Here we present evidences that SREBP-1 regulate muscle protein synthesis through the downregulation of the expression of MYOD1, MYOG and MEF2C factors. In myotubes overexpressing SREBP-1, restoring the expression of myogenic factors prevented atrophy and rescued protein synthesis, without affecting SREBP-1 action on atrogenes and proteolysis. Our results point out the roles of MRFs in the maintenance of the protein content and cell size in adult muscle fibre, and contribute to decipher the mechanisms by which SREBP-1 regulate muscle mass.
authors.affiliation: CarMeN Laboratory, INSERM U1060, INRA 1235, University Lyon1, Oullins, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Dessalle
authors.forename: Vanessa
authors.initials: V
authors.lastname: Euthine
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chanon
authors.forename: Joffrey
authors.initials: J
authors.lastname: Delarichaudy
authors.forename: Isao
authors.initials: I
authors.lastname: Fujii
authors.forename: Sophie
authors.initials: S
authors.lastname: Rome
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Georges
authors.initials: G
authors.lastname: Nemoz
authors.forename: Chantal
authors.initials: C
authors.lastname: Simon
authors.forename: Etienne
authors.initials: E
authors.lastname: Lefai
mesh_terms: D048429:Cell Size; D006801:Humans; D026161:MADS Domain Proteins / Q000378:metabolism; D064326:MEF2 Transcription Factors; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology*; D017570:MyoD Protein / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D018008:Myogenin / Q000378:metabolism; D014176:Protein Biosynthesis; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
chemical_list: D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; C503799:MYOG protein, human; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D034741:RNA, Small Interfering; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1