title: Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle.
abstract: Data from transgenic animal models suggest that exercise-induced autophagy is critical for adaptation to physical training, and that Unc-51 like kinase-1 (ULK1) serves as an important regulator of autophagy. Phosphorylation of ULK1 at Ser(555) stimulates autophagy, whereas phosphorylation at Ser(757) is inhibitory. To determine whether exercise regulates ULK1 phosphorylation in humans in vivo in a nutrient-dependent manner, we examined skeletal muscle biopsies from healthy humans after 1-h cycling exercise at 50% maximal O2 uptake on two occasions: 1) during a 36-h fast, and 2) during continuous glucose infusion at 0.2 kg/h. Physical exercise increased ULK1 phosphorylation at Ser(555) and decreased lipidation of light chain 3B. ULK1 phosphorylation at Ser(555) correlated positively with AMP-activated protein kinase-α Thr(172) phosphorylation and negatively with light chain 3B lipidation. ULK1 phosphorylation at Ser(757) was not affected by exercise. Fasting increased ULK1 and p62 protein expression, but did not affect exercise-induced ULK1 phosphorylation. These data demonstrate that autophagy signaling is activated in human skeletal muscle after 60 min of exercise, independently of nutritional status, and suggest that initiation of autophagy constitutes an important physiological response to exercise in humans.
authors: Research Laboratory for Biochemical Pathology, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark; Medical Research Laboratory, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark;
authors: Andreas Buch
authors: AB
authors: Møller
authors: Medical Research Laboratory, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Aarhus, Denmark; and.
authors: Mikkel Holm
authors: MH
authors: Vendelbo
authors: Research Laboratory for Biochemical Pathology, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark; Medical Research Laboratory, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark;
authors: Britt
authors: B
authors: Christensen
authors: Research Laboratory for Biochemical Pathology, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark; Medical Research Laboratory, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark;
authors: Berthil Forrest
authors: BF
authors: Clasen
authors: Medical Research Laboratory, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark;
authors: Ann Mosegaard
authors: AM
authors: Bak
authors: Medical Research Laboratory, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Internal Medicine and Endocrinology, Aarhus University Hospital, Aarhus, Denmark.
authors: Jens O L
authors: JO
authors: Jørgensen
authors: Medical Research Laboratory, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Internal Medicine and Endocrinology, Aarhus University Hospital, Aarhus, Denmark.
authors: Niels
authors: N
authors: Møller
authors: Research Laboratory for Biochemical Pathology, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark; Medical Research Laboratory, Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark; niels.jessen@clin.au.dk.
authors: Niels
authors: N
authors: Jessen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D001786:Blood Glucose; D018592:Cross-Over Studies; D015444:Exercise / Q000502:physiology*; D005215:Fasting / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D064368:Healthy Volunteers; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009752:Nutritional Status; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011897:Random Allocation; D000071456:Sequestosome-1 Protein; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D047908:Intracellular Signaling Peptides and Proteins; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human; D055372:AMP-Activated Protein Kinases
keywords: ULK1; autophagy signaling; exercise training; human; nutritional status; skeletal muscle