Beta 2 ‐adrenergic agonist clenbuterol increases energy expenditure and fat oxidation, and induces mTOR phosphorylation in skeletal muscle of young healthy men

2020 ◽  
Vol 12 (5) ◽  
pp. 610-618 ◽  
Author(s):  
Søren Jessen ◽  
Sara A. Solheim ◽  
Glenn A. Jacobson ◽  
Kasper Eibye ◽  
Jens Bangsbo ◽  
...  
1999 ◽  
Vol 84 (10) ◽  
pp. 3764-3769
Author(s):  
E. E. Blaak ◽  
M. A. van Baak ◽  
W. H. M. Saris

Abstract The effect of aging on β-adrenergically mediated substrate utilization was investigated in nine young (25.2 ± 1.7 yr old) and eight older males (52.9 ± 2.1 yr old), matched for body weight and body composition. In a first experiment, the nonselectiveβ -agonist isoprenaline (ISO) was infused in increasing standardized doses, and during each infusion period energy expenditure and substrate utilization were determined by indirect calorimetry. In a second experiment, forearm skeletal muscle metabolism was studied during a standardized infusion dose of ISO (19 ng/kg fat-free mass·min). During β-adrenergic stimulation there was an increased carbohydrate oxidation (at an ISO infusion dose of 24 ng/kg fat-free mass·min, 31% vs. 21% of total energy expenditure; P < 0.05) and a decreased fat oxidation (51 vs. 62 of total energy expenditure; P < 0.05) in older compared to young subjects. Skeletal muscle lactate release significantly increased in the older subjects (from −175 ± 32 to −366 ± 66 nmol/100 mL forearm tissue·min), whereas there was no change in young subjects (from− 32 ± 21 to 23 ± 57 nmol/100 mL forearm tissue·min; interaction group × ISO, P < 0.01). Additionally, there was a tendency toward a blunted ISO-induced increase in nonesterified fatty acid uptake in the older subjects (interaction group × ISO, P = 0.062). Thus, middle-aged subjects have a blunted ability to oxidize fat during β-adrenergic stimulation compared to young subjects. This diminished fat oxidation may be an important etiological factor in the age-related increase in body fatness and obesity by favoring fat storage above oxidation.


2021 ◽  
Author(s):  
Ada Admin ◽  
David M Presby ◽  
Michael C Rudolph ◽  
Vanessa D Sherk ◽  
Matthew R Jackman ◽  
...  

Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism genes were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.


2021 ◽  
Author(s):  
Ada Admin ◽  
David M Presby ◽  
Michael C Rudolph ◽  
Vanessa D Sherk ◽  
Matthew R Jackman ◽  
...  

Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism genes were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.


2013 ◽  
Vol 304 (11) ◽  
pp. E1227-E1236 ◽  
Author(s):  
J. Abildgaard ◽  
A. T. Pedersen ◽  
C. J. Green ◽  
N. M. Harder-Lauridsen ◽  
T. P. Solomon ◽  
...  

The purpose of this study was to examine if fat oxidation was affected by menopausal status and to investigate if this could be related to the oxidative capacity of skeletal muscle. Forty-one healthy women were enrolled in this cross-sectional study [premenopausal ( n = 19), perimenopausal ( n = 8), and postmenopausal ( n = 14)]. Estimated insulin sensitivity was obtained from an oral glucose tolerance test. Body composition was measured by dual-energy X-ray absorptiometry and magnetic resonance imaging. Fat oxidation and energy expenditure were measured during an acute exercise bout of 45 min of ergometer biking at 50% of maximal oxygen consumption (V̇o2 max). Muscle biopsies from the vastus lateralis of the quadriceps muscle were obtained before and immediately after the exercise bout. Postmenopausal women had 33% [confidence interval (CI) 95%: 12–55] lower whole body fat oxidation ( P = 0.005) and 19% (CI 95%: 9–22) lower energy expenditure ( P = 0.02) during exercise, as well as 4.28 kg lower lean body mass (LBM) than premenopausal women. Correction for LBM reduced differences in fat oxidation to 23% ( P = 0.05), whereas differences in energy expenditure disappeared ( P = 0.22). No differences between groups were found in mRNA [carnitine palmitoyltransferase I, β-hydroxyacyl-CoA dehydrogenase (β-HAD), peroxisome proliferator-activated receptor-α, citrate synthase (CS), pyruvate dehydrogenase kinase 4, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)], protein [phosphorylated AMP-activated protein kinase (AMPK), vascular endothelial growth factor, pyruvate dehydrogenase-1Eα, cytochrome oxidase I], or enzyme activities (β-HAD, CS) in resting skeletal muscle, except for an increased protein level of cytochrome c in the post- and perimenopausal women relative to premenopausal women. Postmenopausal women demonstrated a trend to a blunted exercise-induced increase in phosphorylation of AMPK compared with premenopausal women ( P = 0.06). We conclude that reduced whole body fat oxidation after menopause is associated with reduced LBM.


2017 ◽  
Vol 77 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Francis B. Stephens

Fat and carbohydrate are the major fuel sources utilised for oxidative, mitochondrial ATP resynthesis during human skeletal muscle contraction. The relative contribution of these two substrates to ATP resynthesis and total energy expenditure during exercise can vary substantially, and is predominantly determined by fuel availability and exercise intensity and duration. For example, the increased ATP demand that occurs with an increase in exercise intensity is met by increases in both fat and carbohydrate oxidation up to an intensity of approximately 60–70 % of maximal oxygen consumption. When exercise intensity increases beyond this workload, skeletal muscle carbohydrate utilisation is accelerated, which results in a reduction and inhibition of the relative and absolute contribution of fat oxidation to total energy expenditure. However, the precise mechanisms regulating muscle fuel selection and underpinning the decline in fat oxidation remain unclear. This brief review will primarily address the theory that a carbohydrate flux-mediated reduction in the availability of muscle carnitine to the mitochondrial enzyme carnitine palmitoyltransferase 1, a rate-limiting step in mitochondrial fat translocation, is a key mechanism for the decline in fat oxidation during high-intensity exercise. This is discussed in relation to recent work in this area investigating fuel metabolism at various exercise intensities and taking advantage of the discovery that skeletal muscle carnitine content can be nutritionally increased in vivo in human subjects.


Metabolism ◽  
2008 ◽  
Vol 57 (9) ◽  
pp. 1198-1203 ◽  
Author(s):  
Peter J.H. Jones ◽  
Stephanie Jew ◽  
Suhad AbuMweis

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 742-P
Author(s):  
KENICHI TANAKA ◽  
HIROKAZU TAKAHASHI ◽  
KAZUYO SASAKI ◽  
KANAKO INOUE ◽  
YAYOI MATSUDA ◽  
...  

2018 ◽  
Vol 28 (12) ◽  
pp. 2494-2504 ◽  
Author(s):  
Sune Dandanell ◽  
Anne-Kristine Meinild-Lundby ◽  
Andreas B. Andersen ◽  
Paul F. Lang ◽  
Laura Oberholzer ◽  
...  

Aging Cell ◽  
2021 ◽  
Vol 20 (2) ◽  
Author(s):  
Carolyn Chee ◽  
Chris E. Shannon ◽  
Aisling Burns ◽  
Anna L. Selby ◽  
Daniel Wilkinson ◽  
...  

1993 ◽  
Vol 265 (3) ◽  
pp. C680-C687 ◽  
Author(s):  
K. K. Azuma ◽  
C. B. Hensley ◽  
M. J. Tang ◽  
A. A. McDonough

The purpose of this study was to determine the pattern of thyroid hormone (triiodothyronine, T3) regulation of the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) alpha- and beta-subunit expression in skeletal muscle, which expresses alpha 1-, alpha 2-, beta 1-, and beta 2-subunits, and compare it with that seen in kidney, which expresses only alpha 1 and beta 1. Three steady states were studied: hypothyroid, euthyroid, and hyperthyroid (hypothyroids injected daily with 1 microgram T3/g body wt for 2-16 days). Protein and mRNA abundance, determined by Western and Northern analysis, were normalized to a constant amount of homogenate protein and total RNA, respectively. In skeletal muscle, there was no change in alpha 1- or beta 1-mRNA or protein levels in the transition from hypothyroid to hyperthyroid. However, alpha 2 was highly regulated; mRNA reached a new steady-state level of fivefold over hypothyroid by 8 days of T3 treatment and protein abundance increased threefold. In addition, beta 2-mRNA and protein were detected in skeletal muscle and were also highly regulated by T3; beta 2-mRNA increased nearly fourfold over hypothyroid level, and beta 2-protein abundance increased over twofold. In kidney in the transition from hypothyroid to hyperthyroid, there were coordinate 1.6-fold increases in both alpha 1- and beta 1-mRNA abundance that predicted the observed changes in alpha 1- and beta 1-protein levels and Na(+)-K(+)-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)


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