title: Effects of energy deficit, dietary protein, and feeding on intracellular regulators of skeletal muscle proteolysis.
abstract: This study was undertaken to characterize the ubiquitin proteasome system (UPS) response to varied dietary protein intake, energy deficit (ED), and consumption of a mixed meal. A randomized, controlled trial of 39 adults consuming protein at 0.8 (recommended dietary allowance [RDA]), 1.6 (2×-RDA), or 2.4 (3×-RDA) g · kg(-1) · d(-1) for 31 d. A 10-d weight maintenance (WM) period was followed by 21 d of 40% ED. Ubiquitin (Ub)-mediated proteolysis and associated gene expression were assessed in the postabsorptive (fasted) and postprandial (fed; 480 kcal, 20 g protein) states after WM and ED by using muscle biopsies, fluorescence-based assays, immunoblot analysis, and real-time qRT-PCR. In the assessment of UPS responses to varied protein intakes, ED, and feeding, the RDA, WM, and fasted measures served as appropriate controls. ED resulted in the up-regulation of UPS-associated gene expression, as mRNA expression of the atrogenes muscle RING finger-1 (MuRF1) and atrogin-1 were 1.2- and 1.3-fold higher (P<0.05) for ED than for WM. However, mixed-meal consumption attenuated UPS-mediated proteolysis, independent of energy status or dietary protein, as the activities of the 26S proteasome subunits β1, β2, and β5 were lower (P<0.05) for fed than for fasted. Muscle protein ubiquitylation was also 45% lower (P<0.05) for fed than for fasted, regardless of dietary protein and energy manipulations. Independent of habitual protein intake and despite increased MuRF1 and atrogin-1 mRNA expression during ED, consuming a protein-containing mixed meal attenuates Ub-mediated proteolysis.
authors: 1Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine, 15 Kansas Street, Building 42, Natick, MA 01760, USA. stefan.pasiakos@us.army.mil.
authors: John W
authors: JW
authors: Carbone
authors: Lee M
authors: LM
authors: Margolis
authors: James P
authors: JP
authors: McClung
authors: Jay J
authors: JJ
authors: Cao
authors: Nancy E
authors: NE
authors: Murphy
authors: Edward R
authors: ER
authors: Sauter
authors: Gerald F
authors: GF
authors: Combs
authors: Andrew J
authors: AJ
authors: Young
authors: Stefan M
authors: SM
authors: Pasiakos
mesh_terms: D000293:Adolescent; D000328:Adult; D001835:Body Weight; D031204:Caloric Restriction; D004044:Dietary Proteins / Q000378:metabolism*; D005215:Fasting; D005260:Female; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D064167:Recommended Dietary Allowances; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D004044:Dietary Proteins; D009124:Muscle Proteins; D025801:Ubiquitin; C440907:FBXO32 protein, human; D063150:Polycomb Repressive Complex 1; C080355:RING1 protein, human; D044843:SKP Cullin F-Box Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: caspase-3; high-protein diets; negative energy balance; ubiquitin proteasome