title: The impact of a 48-h fast on SIRT1 and GCN5 in human skeletal muscle.
abstract: The present study examined the impact of a 48 h fast on the expression and activation status of SIRT1 and GCN5, the relationship between SIRT1/GCN5 and the gene expression of PGC-1α, and the PGC-1α target PDK4 in the skeletal muscle of 10 lean healthy men (age, 22.0 ± 1.5 years; peak oxygen uptake, 47.2 ± 6.7 mL/(min·kg)). Muscle biopsies and blood samples were collected 1 h postprandial (Fed) and following 48 h of fasting (Fasted). Plasma insulin (Fed, 80.8 ± 47.9 pmol/L; Fasted, not detected) and glucose (Fed, 4.36 ± 0.86; Fasted, 3.74 ± 0.25 mmol/L, p = 0.08) decreased, confirming participant adherence to fasting. Gene expression of PGC-1α decreased (p < 0.05, -24%), while SIRT1 and PDK4 increased (p < 0.05, +11% and +1023%, respectively), and GCN5 remained unchanged. No changes were observed for whole-muscle protein expression of SIRT1, GCN5, PGC-1α, or COX IV. Phosphorylation of SIRT1, AMPKα, ACC, p38 MAPK, and PKA substrates as well as nuclear acetylation status was also unaltered. Additionally, nuclear SIRT1 activity, GCN5, and PGC-1α content remained unchanged. Preliminary findings derived from regression analysis demonstrate that changes in nuclear GCN5 and SIRT1 activity/phosphorylation may contribute to the control of PGC-1α, but not PDK4, messenger RNA expression following fasting. Collectively, and in contrast with previous animal studies, our data are inconsistent with the altered activation status of SIRT1 and GCN5 in response to 48 h of fasting in human skeletal muscle.
authors.affiliation: a School of Kinesiology and Health Studies, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Edgett
authors.affiliation: a School of Kinesiology and Health Studies, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: Trisha D
authors.initials: TD
authors.lastname: Scribbans
authors.affiliation: a School of Kinesiology and Health Studies, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: James P
authors.initials: JP
authors.lastname: Raleigh
authors.affiliation: a School of Kinesiology and Health Studies, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: Jennifer B L
authors.initials: JB
authors.lastname: Matusiak
authors.affiliation: b Department of Kinesiology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
authors.forename: Kristen
authors.initials: K
authors.lastname: Boonstra
authors.affiliation: c Department of Emergency Medicine, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Simpson
authors.affiliation: d School of Kinesiology and Health Science, York University, Toronto, ON M3J 1P3, Canada.
authors.forename: Christopher G R
authors.initials: CG
authors.lastname: Perry
authors.affiliation: b Department of Kinesiology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
authors.forename: Joe
authors.initials: J
authors.lastname: Quadrilatero
authors.affiliation: a School of Kinesiology and Health Studies, Queen's University, Kingston, ON K7L 3N6, Canada.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Gurd
mesh_terms: D021581:Active Transport, Cell Nucleus; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D015536:Down-Regulation; D004789:Enzyme Activation; D004790:Enzyme Induction; D005215:Fasting / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010101:Oxygen Consumption; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D019518:Postprandial Period; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D000099224:p300-CBP-Associated Factor
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D051548:Histone Acetyltransferases; D007328:Insulin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011494:Protein Kinases; D056564:Sirtuin 1; C486497:PPARGC1A protein, human; C501179:KAT2A protein, human; D000099224:p300-CBP-Associated Factor; C403287:pyruvate dehydrogenase kinase 4; C447939:SIRT1 protein, human
keywords: GCN5; KAT2A; PGC-1α; SIRT1; fasting; jeûne; muscle squelettique; skeletal muscle