Formoterol, a Highly β2-Selective Agonist, Induces Gender-Dimorphic Whole Body Leucine Metabolism in Humans

Lee, Paul; Birzniece, Vita; Umpleby, AM; Poljak, Anne

doi:10.1016/j.metabol.2014.12.005

Cited by 20 publications

(37 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this, 4 weeks of oral terbutaline treatment has been shown to increase whole‐body lean mass by ~1.7 kg and cross‐sectional area of MHC I and MHC II muscle fibers by 17 and 15%, respectively, in moderately trained men . The hypertrophic effect of beta 2 ‐adrenergic agonists is related to increased muscle protein turnover in favor of protein incorporation leading to a more positive protein net balance in both men and women . However, not all studies have observed skeletal muscle hypertrophy following chronic beta 2 ‐adrenergic agonist administration, which may be related to differences in dosing protocol, drug adherence and habitual activity level and life‐style.…”

Section: Discussionmentioning

confidence: 86%

Effect of beta₂‐adrenergic agonist and resistance training on maximal oxygen uptake and muscle oxidative enzymes in men

Lemminger

Jessen

Habib

et al. 2019

Scandinavian Med Sci Sports

View full text Add to dashboard Cite

While beta2‐adrenoceptor stimulation has been shown to increase lean mass and to alter metabolic properties of skeletal muscle, adaptations in muscle oxidative enzymes and maximal oxygen uptake (trueV˙O2max) in response to beta2‐adrenergic agonist treatment are inadequately explored in humans, particularly in association with resistance training. Herein, we investigated beta2‐adrenergic‐induced changes in trueV˙O2max, leg and arm composition, and muscle content of oxidative enzymes in response to treatment with the selective beta2‐adrenergic agonist terbutaline with and without concurrent resistance training in young men. Forty‐six subjects were randomized to 4 weeks of lifestyle maintenance (n = 23) or resistance training (n = 23). Within the lifestyle maintenance and resistance training group, subjects received daily terbutaline (8 × 0.5 mg) (n = 13) or placebo (n = 10) treatment. No apparent treatment by training interactions was observed during the study period. Terbutaline increased leg and arm lean mass with the intervention, whereas no treatment differences were observed in absolute trueV˙O2max and incremental peak power output (iPPO). Treatment main effects were observed for trueV˙O2‐reserve (P < .05), trueV˙O2max relative to body mass (P < .05), trueV˙O2max relative to leg lean mass (P < .01), and iPPO relative to leg lean mass, in which terbutaline had a negative effect compared with placebo. Furthermore, content of electron transport chain complex I‐V decreased by 11% (P < .05) for terbutaline compared with placebo. Accordingly, chronic treatment with the selective beta2‐adrenergic agonist terbutaline may negatively affect trueV˙O2max and iPPO in relative terms, but not in absolute.

show abstract

Section: Discussionmentioning

confidence: 86%

Effect of beta₂‐adrenergic agonist and resistance training on maximal oxygen uptake and muscle oxidative enzymes in men

Lemminger

Jessen

Habib

et al. 2019

Scandinavian Med Sci Sports

View full text Add to dashboard Cite

show abstract

“…From the above results the activation of hormone sensitive lipase must be based on the adrenoceptor-β 2 -agonistic activity. It is well known fact that adrenoceptor-β 2 -agonistic activity is linked to the activation of hormone-sensitive lipase in adipocytes and also to the activation of β-oxidation of fatty acids in muscle cells (Otton et al ., 1984; Lee et al ., 2015). …”

Section: Resultsmentioning

confidence: 99%

“…3B). Hence, the highly activated spontaneous locomotive activity of capsanthin group must be due to the increased production of ATP as the result of increased oxidation of fatty acids in muscle cell (Otton et al ., 1984; Lee et al ., 2015). The enhanced β-oxidation of fatty acids could be exemplified by the sudden increase of ketone body in the serum of mice fed more than 10 μmol of capsanthin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Capsanthin Inhibits both Adipogenesis in 3T3-L1 Preadipocytes and Weight Gain in High-Fat Diet-Induced Obese Mice

Jo¹,

Kim²,

Choi³

et al. 2017

Biomolecules & Therapeutics

View full text Add to dashboard Cite

Adipogenesis in murine preadipocyte 3T3L-1 has been used as a model system to study anti-obese bioactive molecules. During adipogenesis in 3T3-L1 preadipocytes, we found that capsanthin inhibited adipogenesis (IC50; 2.5 μM) and also showed lipolytic activity in differentiated adipocytes from the preadipocytes (ED50; 872 nM). We identified that the pharmacological activity of capsanthin on adipogenesis in 3T3-L1 was mainly due to its adrenoceptor-β2-agonistic activity. In high-fat diet animal model study, capsanthin significantly enhanced spontaneous locomotive activities together with progressive weight-loss. The capsanthin-induced activation of kinetic behavior in mice was associated with the excessive production of ATP initiated by both the enhanced lipolytic activity together with accelerated oxidation of fatty acids due to the adrenoceptor β2-agonistic activity of capsanthin. Capsanthin also dose-dependently increased adiponectin and p-AMPK activity in high fat diet animals, suggesting that capsanthin has both anti-obesity and insulin sensitizing activities.

show abstract

“…Stimulation of muscle beta 2 ‐adrenoceptors with selective agonists modulates myocellular excitation‐contraction coupling and metabolism, which appear mediated by cAMP/protein kinase A (PKA)‐dependent signaling . Furthermore, beta 2 ‐agonists stimulate muscle protein turnover and growth . Given their anabolic and lipolytic properties, beta 2 ‐agonists have attracted interest as potential treatment in muscle wasting disorders and obesity …”

Section: Introductionmentioning

confidence: 99%

Beta₂‐adrenergic ligand racemic formoterol exhibits enantioselective disposition in blood and skeletal muscle of humans, and elicits myocellular PKA signaling at therapeutic inhaled doses

Hostrup

Narkowicz

Habib

et al. 2019

Drug Testing and Analysis

View full text Add to dashboard Cite

While studies have demonstrated substantial differences in beta2‐adrenergic agonist enantiomer pharmacology, enantioselective disposition of long‐acting beta2‐adrenergic ligand racemic (rac)‐formoterol in blood is inadequately explored after inhaled therapy given analytical challenges. Furthermore, information on enantioselective disposition and partitioning of beta2‐adrenergic agonist in skeletal muscle is absent despite its promising data on muscle anabolism in humans. Using a sensitive ultra‐high performance liquid chromatography−mass spectrometry (UPLC−MS/MS) assay, we determined disposition of (R,R)‐formoterol and (S,S)‐formoterol in plasma and skeletal muscle samples from 11 non‐asthmatic men who had inhaled rac‐formoterol at therapeutic doses (2 × 27 μg). Mean (SD) concentrations of (R,R)‐ and (S,S)‐formoterol in plasma and in muscle biopsies of the vastus lateralis 1 hour after inhalation of formoterol were 31 (15) and 45 (18) pg × mL−1 for (R,R)‐formoterol and (S,S)‐formoterol, respectively, in plasma, and 0.56 (0.32) and 0.51 (0.29) pg × mgwet wt−1, respectively, in muscle. Formoterol exhibited different enantioselective disposition in plasma and muscle (p < 0.0001). In plasma, mean log (R,R):(S,S)‐formoterol ratio was lower than 0 [−0.17(0.07), p < 0.0001], whereas in muscle, mean log (R,R):(S,S)‐formoterol ratio was slightly higher than 0 [0.04(0.07), p < 0.05]. Log (R,R):(S,S)‐formoterol ratio in muscle was related to muscle fiber‐type composition. Furthermore, formoterol induced an approximately two‐fold increase in muscle p‐PKASer/thr phosphorylation (p < 0.01), indicating a substantial beta2‐adrenergic response. Collectively, these findings suggest that formoterol exhibits modest enantioselective disposition in plasma after inhaled therapy in humans, which appear related to a greater (R,R)‐enantiomer disposition in skeletal muscle that may be dependent on fiber‐type composition.

show abstract

Formoterol, a Highly β2-Selective Agonist, Induces Gender-Dimorphic Whole Body Leucine Metabolism in Humans

Cited by 20 publications

References 31 publications

Effect of beta₂‐adrenergic agonist and resistance training on maximal oxygen uptake and muscle oxidative enzymes in men

Effect of beta₂‐adrenergic agonist and resistance training on maximal oxygen uptake and muscle oxidative enzymes in men

Capsanthin Inhibits both Adipogenesis in 3T3-L1 Preadipocytes and Weight Gain in High-Fat Diet-Induced Obese Mice

Beta₂‐adrenergic ligand racemic formoterol exhibits enantioselective disposition in blood and skeletal muscle of humans, and elicits myocellular PKA signaling at therapeutic inhaled doses

Contact Info

Product

Resources

About

Formoterol, a Highly β2-Selective Agonist, Induces Gender-Dimorphic Whole Body Leucine Metabolism in Humans

Cited by 20 publications

References 31 publications

Effect of beta2‐adrenergic agonist and resistance training on maximal oxygen uptake and muscle oxidative enzymes in men

Effect of beta2‐adrenergic agonist and resistance training on maximal oxygen uptake and muscle oxidative enzymes in men

Capsanthin Inhibits both Adipogenesis in 3T3-L1 Preadipocytes and Weight Gain in High-Fat Diet-Induced Obese Mice

Beta2‐adrenergic ligand racemic formoterol exhibits enantioselective disposition in blood and skeletal muscle of humans, and elicits myocellular PKA signaling at therapeutic inhaled doses

Contact Info

Product

Resources

About

Effect of beta₂‐adrenergic agonist and resistance training on maximal oxygen uptake and muscle oxidative enzymes in men

Effect of beta₂‐adrenergic agonist and resistance training on maximal oxygen uptake and muscle oxidative enzymes in men

Beta₂‐adrenergic ligand racemic formoterol exhibits enantioselective disposition in blood and skeletal muscle of humans, and elicits myocellular PKA signaling at therapeutic inhaled doses