title: Effect of birth weight and 12 weeks of exercise training on exercise-induced AMPK signaling in human skeletal muscle.
abstract: Subjects with a low birth weight (LBW) display increased risk of developing type 2 diabetes (T2D). We hypothesized that this is associated with defects in muscle adaptations following acute and regular physical activity, evident by impairments in the exercise-induced activation of AMPK signaling. We investigated 21 LBW and 21 normal birth weight (NBW) subjects during 1 h of acute exercise performed at the same relative workload before and after 12 wk of exercise training. Multiple skeletal muscle biopsies were obtained before and after exercise. Protein levels and phosphorylation status were determined by Western blotting. AMPK activities were measured using activity assays. Protein levels of AMPKα1 and -γ1 were significantly increased, whereas AMPKγ3 levels decreased with training independently of group. The LBW group had higher exercise-induced AMPK Thr(172) phosphorylation before training and higher exercise-induced ACC2 Ser(221) phosphorylation both before and after training compared with NBW. Despite exercise being performed at the same relative intensity (65% of Vo2peak), the acute exercise response on AMPK Thr(172), ACC2 Ser(221), AMPKα2β2γ1, and AMPKα2β2γ3 activities, GS activity, and adenine nucleotides as well as hexokinase II mRNA levels were all reduced after exercise training. Increased exercise-induced muscle AMPK activation and ACC2 Ser(221) phosphorylation in LBW subjects may indicate a more sensitive AMPK system in this population. Long-term exercise training may reduce the need for AMPK to control energy turnover during exercise. Thus, the remaining γ3-associated AMPK activation by acute exercise after exercise training might be sufficient to maintain cellular energy balance.
authors.affiliation: Steno Diabetes Center, Gentofte, Copenhagen, Denmark;
authors.forename: Brynjulf
authors.initials: B
authors.lastname: Mortensen
authors.forename: Janne R
authors.initials: JR
authors.lastname: Hingst
authors.forename: Nicklas
authors.initials: N
authors.lastname: Frederiksen
authors.forename: Rikke W W
authors.initials: RW
authors.lastname: Hansen
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Christiansen
authors.forename: Ninna
authors.initials: N
authors.lastname: Iversen
authors.forename: Martin
authors.initials: M
authors.lastname: Friedrichsen
authors.forename: Jesper B
authors.initials: JB
authors.lastname: Birk
authors.forename: Henriette
authors.initials: H
authors.lastname: Pilegaard
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hellsten
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D001724:Birth Weight / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007230:Infant, Low Birth Weight / Q000502:physiology*; D007231:Infant, Newborn; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult
chemical_list: D055372:AMP-Activated Protein Kinases
keywords: AMPK; exercise training; fetal programming