β-Hydroxy-β-methylbutyrate (HMB) prevents sepsis-induced diaphragm dysfunction in mice

Supinski, Gerald S.; Callahan, Leigh Ann

doi:10.1016/j.resp.2014.02.015

Cited by 20 publications

(18 citation statements)

References 30 publications

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“…Beneficial effects of HMB in human subjects have been reported in several muscledeconditioning conditions characterized by a loss of muscle mass and a decrease in muscle strength and physical performance, for example, cancer cachexia (May et al, 2002), AIDS (Clark et al, 2000), chronic obstructive pulmonary disease (Hsieh et al, 2006) and aging (Baier et al, 2009;Deutz et al, 2013;Flakoll et al, 2004;Hsieh et al, 2010;May et al, 2002;Stout et al, 2013;Vukovich et al, 2001). Efficiency of HMB in various muscle-deconditioning conditions in rodents and cell lines has also been reported, e.g., experimental models of cachexia (Aversa et al, 2011;Caperuto et al, 2007;Eley et al, 2007;Mirza et al, 2014b;Nunes et al, 2008;Smith et al, 2005), glucocorticoid treatments (Aversa et al, 2012;Baptista et al, 2013;Giron et al, 2015;Nunes et al, 2013), and experimental models of sepsis and endotoxemia (Eley et al, 2008a;Kovarik et al, 2010;Supinski and Callahan, 2014) in response to muscle-wasting treatments such as TNF-α and angiotensin II (Eley et al, 2008a, b), a mouse model of Duchenne muscular dystrophy (Payne et al, 2006), and hypokinesia and hypodynamia models (HU or immobilization) (Alway et al, 2013;Baptista et al, 2013;Hao et al, 2011;Mirza et al, 2014b). In animals, effects of HMB during aging have been studied only in combination with other muscle-deconditioning circumstances (Alway et al, 2013;Hao et al, 2011), and specific studies are needed.…”

Section: Hmb: a Very Potent Strategy Against Various Muscle-wasting Cmentioning

confidence: 86%

Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention

Brioche

Pagano

et al. 2016

Molecular Aspects of Medicine

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Identification of cost-effective interventions to maintain muscle mass, muscle strength, and physical performance during muscle wasting and aging is an important public health challenge. It requires understanding of the cellular and molecular mechanisms involved. Muscle-deconditioning processes have been deciphered by means of several experimental models, bringing together the opportunities to devise comprehensive analysis of muscle wasting. Studies have increasingly recognized the importance of fatty infiltrations or intermuscular adipose tissue for the age-mediated loss of skeletal-muscle function and emphasized that this new important factor is closely linked to inactivity. The present review aims to address three main points. We first mainly focus on available experimental models involving cell, animal, or human experiments on muscle wasting. We next point out the role of intermuscular adipose tissue in muscle wasting and aging and try to highlight new findings concerning aging and muscle-resident mesenchymal stem cells called fibro/adipogenic progenitors by linking some cellular players implicated in both FAP fate modulation and advancing age. In the last part, we review the main data on the efficiency and molecular and cellular mechanisms by which exercise, replacement hormone therapies, and β-hydroxy-β-methylbutyrate prevent muscle wasting and sarcopenia. Finally, we will discuss a potential therapeutic target of sarcopenia: glucose 6-phosphate dehydrogenase.

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Section: Hmb: a Very Potent Strategy Against Various Muscle-wasting Cmentioning

confidence: 86%

Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention

Brioche

Pagano

et al. 2016

Molecular Aspects of Medicine

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“…Diaphragmatic weakness leading to acute respiratory failure is associated with increased expression of pro-inflammatory cytokines resulting from a systemic inflammatory response syndrome [ 14 , 15 , 25 ]. Cytokine levels in amniotic fluid and fetal cord blood increase in response to chorioamnionitis in both clinical and animal studies [ 1 , 21 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 Receptor Antagonist Protects against Lipopolysaccharide Induced Diaphragm Weakness in Preterm Lambs

et al. 2015

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Chorioamnionitis (inflammation of the fetal membranes) is strongly associated with preterm birth and in utero exposure to inflammation significantly impairs contractile function in the preterm lamb diaphragm. The fetal inflammatory response to intra-amniotic (IA) lipopolysaccharide (LPS) is orchestrated via interleukin 1 (IL-1). We aimed to determine if LPS induced contractile dysfunction in the preterm diaphragm is mediated via the IL-1 pathway. Pregnant ewes received IA injections of recombinant human IL-1 receptor antagonist (rhIL-1ra) (Anakinra; 100 mg) or saline (Sal) 3 h prior to second IA injections of LPS (4 mg) or Sal at 119d gestational age (GA). Preterm lambs were killed after delivery at 121d GA (term = 150 d). Muscle fibres dissected from the right hemi-diaphragm were mounted in an in vitro muscle test system for assessment of contractile function. The left hemi-diaphragm was snap frozen for molecular and biochemical analyses. Maximum specific force in lambs exposed to IA LPS (Sal/LPS group) was 25% lower than in control lambs (Sal/Sal group; p=0.025). LPS-induced diaphragm weakness was associated with higher plasma IL-6 protein, diaphragm IL-1β mRNA and oxidised glutathione levels. Pre-treatment with rhIL-1ra (rhIL-1ra/LPS) ameliorated the LPS-induced diaphragm weakness and blocked systemic and local inflammatory responses, but did not prevent the rise in oxidised glutathione. These findings indicate that LPS induced diaphragm dysfunction is mediated via IL-1 and occurs independently of oxidative stress. Therefore, the IL-1 pathway represents a potential therapeutic target in the management of impaired diaphragm function in preterm infants.

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“…An increase of caspase-3 activity in different body sites in septic animal models has been found [7][8][9][10][11][12][13][14][15][16][17][18]. Besides, higher caspase-3 activity has been found in lymphocytes of septic patients compared to healthy controls [19][20][21], in spleen samples of septic patients (post mortem obtained) comparted to nonseptic patients (obtained from emergent splenectomy due to bleeding) [22], and in plasma of septic patients compared to non-septic patients [23].…”

Section: Introductionmentioning

confidence: 92%

Sustained high serum caspase-3 concentrations and mortality in septic patients

Lorente

Martı́n

Pérez-Cejas

et al. 2017

Eur J Clin Microbiol Infect Dis

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Caspase-3 is the main executor of the apoptotic process. Higher serum caspase-3 concentrations in non-survivor compared to survivor septic patients have been found. The objectives of this work (with the increase of sample size to 308 patients, and the determination of serum caspase-3 concentrations also on days 4 and 8 of diagnosis of severe sepsis) were to know whether an association between serum caspase-3 concentrationss during the first week, degree of apoptosis, sepsis severity, and sepsis mortality exists. We collected serum samples of 308 patients with severe sepsis from eight intensive care units on days 1, 4 and 8 to measure concentrations of caspase-3 and caspase-cleaved cytokeratin (CCCK)-18 (to assess degree of apoptosis). End point was 30-day mortality. We found higher serum concentrations of caspase-3 and CCCK-18 in non-survivors compared to survivors on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001). We found an association between serum caspase-3 concentrations on days 1, 4 and 8 of severe sepsis diagnosis and serum CCCK-18 concentrations (p < 0.001), SOFA (p < 0.001), serum acid lactic concentrations (p < 0.001), and 30-day sepsis mortality (p < 0.001). The new findings of this work were that an association between serum caspase-3 concentrations during the first week, apoptosis degree, sepsis severity, and sepsis mortality exists.

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β-Hydroxy-β-methylbutyrate (HMB) prevents sepsis-induced diaphragm dysfunction in mice

Cited by 20 publications

References 30 publications

Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention

Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention

Interleukin-1 Receptor Antagonist Protects against Lipopolysaccharide Induced Diaphragm Weakness in Preterm Lambs

Sustained high serum caspase-3 concentrations and mortality in septic patients

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