title: Formoterol, a highly β2-selective agonist, induces gender-dimorphic whole body leucine metabolism in humans.
abstract: OBJECTIVE
  Formoterol is a β(2)-selective agonist that enhances protein anabolism in rodents. Whether formoterol imparts anabolic benefits in humans is unknown. The objective of the study was to investigate the effects of formoterol on whole body protein rates of turnover, oxidative loss and synthesis.
  
  
  METHODS
  Open label intervention study.
  
  
  METHODS
  Fifteen healthy adults (8 men).
  
  
  METHODS
  Volunteers were treated with oral formoterol 160 μg/day for one week. Changes in leucine turnover (LRa; index of protein breakdown), oxidation (Lox; irreversible protein loss) and incorporation into protein (LIP; index of protein synthesis) were assessed using the whole body 1-[(13)C]leucine turnover technique before/after treatment.
  
  
  RESULTS
  LRa, Lox and LIP correlated significantly with lean body mass (LBM). LRa, adjusted for LBM was significantly higher (P<0.05, 160±6 vs 109±3 μmol/min) in men but not fractional Lox and LIP (expressed as a proportion of LRa). Formoterol reduced LRa (-9±4%) in men but stimulated LRa (9±3%) in women. Formoterol significantly reduced (P<0.05) fractional Lox, an effect greater in women (-4±1 vs -1±1 %). It stimulated fractional LIP in women (∆4±1%, P<0.05) but not in men (∆1±1%). Formoterol induced an absolute anabolic effect that was greater in women (30 vs 8%). Heart rate, systolic and diastolic blood pressures were unaffected.
  
  
  CONCLUSIONS
  In a therapeutic dose, formoterol stimulates protein anabolism in humans. It induced gender-dimorphic effects on protein turnover and on the partitioning of amino acids from oxidative loss toward protein synthesis, effects that are greater in women than in men. Formoterol holds promise as a treatment for sarcopenia.
authors: Pituitary Research Unit, Garvan Institute of Medical Research, Sydney, Australia; Department of Endocrinology, St Vincent's Hospital, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors: Paul
authors: P
authors: Lee
authors: Pituitary Research Unit, Garvan Institute of Medical Research, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors: Vita
authors: V
authors: Birzniece
authors: Diabetes and Metabolic Medicine, Faculty of Health and Medical Sciences, University of Surrey, United Kingdom.
authors: A Margot
authors: AM
authors: Umpleby
authors: Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia; School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors: Anne
authors: A
authors: Poljak
authors: Pituitary Research Unit, Garvan Institute of Medical Research, Sydney, Australia; Department of Endocrinology, St Vincent's Hospital, Sydney, Australia; Faculty of Medicine, University of New South Wales, Sydney, Australia. Electronic address: k.ho@uq.edu.au.
authors: Ken K Y
authors: KK
authors: Ho
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D007930:Leucine / Q000378:metabolism*; D008297:Male; D014176:Protein Biosynthesis / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects; D012727:Sex Characteristics
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D004983:Ethanolamines; D011506:Proteins; D007930:Leucine; D000068759:Formoterol Fumarate
keywords: Beta-agonist; Formoterol; Leucine turnover; Sarcopenia; Skeletal muscle