Effect of Atorvastatin on Energy Expenditure and Skeletal Muscle Oxidative Metabolism at Rest and During Exercise

Chung, Jin Ho; Brass, EP; Rg, Ulrich; Hiatt, WR

doi:10.1038/sj.clpt.6100264

Cited by 20 publications

(26 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in line with the recent findings demonstrating that the main thermogenic capacity in mice is present in brown and not in brite adipocytes (Kalinovich et al, 2017), and fits with (E) Effect of Pggt1b deletion on energy expenditure (wild-type n = 4; CreERT2 n = 7). findings of several studies, which did not observe changes in energy expenditure upon statin treatment (Chung et al, 2008;Panayiotou et al, 2013). It is important, however, to point out that we used statins as a pharmacological tool to achieve short-term inhibition of the mevalonate pathway.…”

Section: Discussionmentioning

confidence: 82%

Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation

Baláž¹,

Becker²,

Balážová³

et al. 2019

Cell Metabolism

View full text Add to dashboard Cite

Correspondence matthias.betz@usb.ch (M.J.B.), irene.burger@usz.ch (I.A.B.), christian-wolfrum@ethz.ch (C.W.) In Brief Through genetic and pharmacological in vivo and in vitro approaches, Balaz et al. show that the mevalonate pathway is important for adipocyte browning. The importance of this pathway is supported by a retrospective clinical study and a small volunteer trial with fluvastatin. The authors identify geranylgeranyl pyrophosphate as the key mevalonate intermediate driving adipocyte browning. SUMMARYRecent research focusing on brown adipose tissue (BAT) function emphasizes its importance in systemic metabolic homeostasis. We show here that genetic and pharmacological inhibition of the mevalonate pathway leads to reduced human and mouse brown adipocyte function in vitro and impaired adipose tissue browning in vivo. A retrospective analysis of a large patient cohort suggests an inverse correlation between statin use and active BAT in humans, while we show in a prospective clinical trial that fluvastatin reduces thermogenic gene expression in human BAT. We identify geranylgeranyl pyrophosphate as the key mevalonate pathway intermediate driving adipocyte browning in vitro and in vivo, whose effects are mediated by geranylgeranyltransferases (GGTases), enzymes catalyzing geranylgeranylation of small GTP-binding proteins, thereby regulating YAP1/TAZ signaling through F-actin modulation. Conversely, adipocyte-specific ablation of GGTase I leads to impaired adipocyte browning, reduced energy expenditure, and glucose intolerance under obesogenic conditions, highlighting the importance of this pathway in modu-lating brown adipocyte functionality and systemic metabolism.

show abstract

Section: Discussionmentioning

confidence: 82%

Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation

Baláž¹,

Becker²,

Balážová³

et al. 2019

Cell Metabolism

View full text Add to dashboard Cite

show abstract

“…The separate efficacy of either exercise or statins in primary CVD prevention has been well established [31,32]. To demonstrate the suitability of statins for subjects without cardiovascular disease, previous studies have reported that statins did not decrease VO 2 peak [33]. However, these results have to be taken with caution since they are based on a small sample size of 28.…”

Section: Discussionmentioning

confidence: 99%

Statins are related to impaired exercise capacity in males but not females

et al. 2017

View full text Add to dashboard Cite

BackgroundExercise and statins reduce cardiovascular disease (CVD). Exercise capacity may be assessed using cardiopulmonary exercise testing (CPET). Whether statin medication is associated with CPET parameters is unclear. We investigated if statins are related with exercise capacity during CPET in the general population.MethodsCross-sectional data of two independent cohorts of the Study of Health in Pomerania (SHIP) were merged (n = 3,500; 50% males). Oxygen consumption (VO2) at peak exercise (VO2peak) and anaerobic threshold (VO2@AT) was assessed during symptom-limited CPET. Two linear regression models related VO2peak with statin usage were calculated. Model 1 adjusted for age, sex, previous myocardial infarction, and physical inactivity and model 2 additionally for body mass index, smoking, hypertension, diabetes and estimated glomerular filtration rate. Propensity score matching was used for validation.ResultsStatin usage was associated with lower VO2peak (no statin: 2336; 95%-confidence interval [CI]: 2287–2,385 vs. statin 2090; 95%-CI: 2,031–2149 ml/min; P < .0001) and VO2@AT (no statin: 1,172; 95%-CI: 1,142–1,202 vs. statin: 1,111; 95%-CI: 1,075–1,147 ml/min; P = .0061) in males but not females (VO2peak: no statin: 1,467; 95%-CI: 1,417–1,517 vs. statin: 1,503; 95%-CI: 1,426–1,579 ml/min; P = 1.00 and VO2@AT: no statin: 854; 95%-CI: 824–885 vs. statin 864; 95%-CI: 817–911 ml/min; P = 1.00). Model 2 revealed similar results. Propensity scores analysis confirmed the results.ConclusionIn the general population present statin medication was related with impaired exercise capacity in males but not females. Sex specific effects of statins on cardiopulmonary exercise capacity deserve further research.

show abstract

“…A recent study that randomized 37 patients who were overweight or obese and at risk of metabolic syndrome to 12 weeks of aerobic ET with or without simvastatin demonstrated attenuated cardiorespiratory fitness responses and decreased skeletal muscle mitochondrial content in patients treated with simvastatin (8). However, 2 small studies evaluated the effects of 40 mg daily atorvastatin and 80 mg daily simvastatin in healthy subjects on maximal exercise capacity over 8 and 12 weeks of therapy, respectively, demonstrating no effect on maximal oxygen consumption (25,26). A prospective study that evaluated 1,201 patients with coronary artery disease undergoing 12 weeks of CR after an acute cardiac event found no effect of statin therapy on ET response (27).…”

Section: Discussionmentioning

confidence: 99%

Statins and Exercise Training Response in Heart Failure Patients

Kelly

Dunning

Schulte

et al. 2016

JACC: Heart Failure

View full text Add to dashboard Cite

OBJECTIVES The aim of this study was to assess for a treatment interaction between statin use and ET response. BACKGROUND Recent data suggest that statins may attenuate exercise training (ET) response, but limited data exist in patients with heart failure (HF). METHODS HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) was a randomized trial of 2,331 patients with chronic HF with ejection fraction ≤35% who were randomized to usual care with or without ET. We evaluated whether there was a treatment interaction between statins and ET response for the change in quality of life and aerobic capacity (peak oxygen consumption and 6-min walk distance) from baseline to 3 months. We also assessed for a treatment interaction among atorvastatin, simvastatin, and pravastatin and change in these endpoints with ET. Multiple linear regression analyses were performed for each endpoint, adjusting for baseline covariates. RESULTS Of 2,331 patients in the HF-ACTION trial, 1,353 (58%) were prescribed statins at baseline. Patients treated with statins were more likely to be older men with ischemic HF etiology but had similar use of renin angiotensin system blockers and beta-blockers. There was no evidence of a treatment interaction between statin use and ET on changes in quality of life or exercise capacity, nor was there evidence of differential association between statin type and ET response for these endpoints (all p values >0.05). CONCLUSIONS In a large chronic HF cohort, there was no evidence of a treatment interaction between statin use and short-term change in aerobic capacity and quality of life with ET. These findings contrast with recent reports of an attenuation in ET response with statins in a different population, highlighting the need for future prospective studies. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437)

show abstract

Effect of Atorvastatin on Energy Expenditure and Skeletal Muscle Oxidative Metabolism at Rest and During Exercise

Cited by 20 publications

References 42 publications

Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation

Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation

Statins are related to impaired exercise capacity in males but not females

Statins and Exercise Training Response in Heart Failure Patients

Contact Info

Product

Resources

About