title: Ribosome abundance regulates the recovery of skeletal muscle protein mass upon recuperation from postnatal undernutrition in mice.
abstract: Nutritionally-induced growth faltering in the perinatal period has been associated with reduced adult skeletal muscle mass; however, the mechanisms responsible for this are unclear. To identify the factors that determine the recuperative capacity of muscle mass, we studied offspring of FVB mouse dams fed a protein-restricted diet during gestation (GLP) or pups suckled from postnatal day 1 (PN1) to PN11 (E-UN), or PN11 to PN22 (L-UN) on protein-restricted or control dams. All pups were refed under control conditions following the episode of undernutrition. Before refeeding, and 2, 7 and 21 days later, muscle protein synthesis was measured in vivo. There were no long-term deficits in protein mass in GLP and E-UN offspring, but in L-UN offspring muscle protein mass remained significantly smaller even after 18 months (P < 0.001). E-UN differed from L-UN offspring by their capacity to upregulate postprandial muscle protein synthesis when refed (P < 0.001), a difference that was attributable to a transient increase in ribosomal abundance, i.e. translational capacity, in E-UN offspring (P < 0.05); translational efficiency was similar across dietary treatments. The postprandial phosphorylation of Akt and extracellular signal-regulated protein kinases were similar among treatments. However, activation of the ribosomal S6 kinase 1 via mTOR (P < 0.02), and total upstream binding factor abundance were significantly greater in E-UN than L-UN offspring (P < 0.02). The results indicate that the capacity of muscles to recover following perinatal undernutrition depends on developmental age as this establishes whether ribosome abundance can be enhanced sufficiently to promote the protein synthesis rates required to accelerate protein deposition for catch-up growth.
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA martaf@bcm.edu.
authors.forename: Marta L
authors.initials: ML
authors.lastname: Fiorotto
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Davis
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Horacio A
authors.initials: HA
authors.lastname: Sosa
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Villegas-Montoya
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Irma
authors.initials: I
authors.lastname: Estrada
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Fleischmann
mesh_terms: D000367:Age Factors; D000818:Animals; D001835:Body Weight; D001846:Bone Development; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D044342:Malnutrition / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D011247:Pregnancy; D014176:Protein Biosynthesis; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism
chemical_list: D007328:Insulin; D009124:Muscle Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D012333:RNA, Messenger; D013002:Somatomedins; C063844:transcription factor UBF