Formoterol, a Highly beta-Selective Agonist, Induces Gender-Dimorphic Whole Body Leucine Metabolism in Humans
OBJECTIVE: Formoterol is a beta2-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. DESIGN: Open label intervention study. PATIENTS: Fifteen healthy adults (8 men). MEASUREMENTS: Volunteers were treated with oral formoterol 160mug/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-[13C]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+/-3mumol/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. CONCLUSION: 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.
|ISBN||1532-8600 (Electronic) 0026-0495 (Linking)|
|Authors||Lee, P.; Birzniece, V.; Umpleby, A. M.; Poljak, A.; Ho, K. K.;|
|Responsible Garvan Author|
|Publisher Name||METABOLISM-CLINICAL AND EXPERIMENTAL|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/25650070|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12675|