RESUMEN
AIMS: Patients with chronic obstructive pulmonary disease (COPD) frequently exhibit an inability to maintain postural balance. However, the contribution of increased intestinal permeability or leaky gut to the postural imbalance in COPD is not known. METHODS: We measured plasma zonulin, a marker of leaky gut, with relevance to postural balance in male controls (n = 70) and patients with mild (n = 67), moderate (n = 66), and severe (n = 58) COPD. We employed a short physical performance battery to evaluate postural balance in supine, tandem, and semi-tandem positions. We also measured handgrip strength (HGS), gait speed, plasma c-reactive proteins (CRP), and 8-isoprostanes as potential mechanistic connections between postural imbalance and leaky gut. RESULTS: COPD patients demonstrated higher plasma zonulin, CRP, and 8-isoprostanes levels and lower balance, HGS, and gait speed than controls (all p < 0.05). These findings were more robust in patients with moderate and severe than mild COPD. In addition, plasma zonulin exhibited significant potential in diagnosing poor balance, low HGS, and gait speed in COPD patients (all p < 0.05). We also found significant correlations of plasma zonulin with CRP and 8-isoprostanes, providing heightened inflammation and oxidative stress as mechanistic connections between leaky gut and postural imbalance. CONCLUSION: Plasma zonulin may be helpful in evaluating postural imbalance in COPD patients. Repairing intestinal leaks can be a therapeutic target to improve postural control in COPD.
Asunto(s)
Biomarcadores , Proteína C-Reactiva , Haptoglobinas , Equilibrio Postural , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/sangre , Anciano , Persona de Mediana Edad , Proteína C-Reactiva/metabolismo , Biomarcadores/sangre , Fuerza de la Mano , Precursores de Proteínas/sangre , Toxina del Cólera/sangre , Estudios de Casos y Controles , Permeabilidad , Dinoprost/análogos & derivadosRESUMEN
Sarcopenia is related to disease severity in chronic kidney disease (CKD) patients; however, its pathophysiology remains poorly known. We investigated the associations of biomarkers of intestinal leak with sarcopenia in various stages of CKD. We recruited 61-76-year-old male controls and patients with various stages of CKD (n = 36-57/group) for measuring plasma lipopolysaccharide-binding protein (LBP) and zonulin (markers of intestinal leak), handgrip strength (HGS), skeletal mass index (SMI), and gait speed (markers of sarcopenia), and short physical performance battery (SPPB; marker of physical capacity). CKD stages 4 and 5 were associated with lower HGS, SMI, gait speed, and cumulative SPPB scores and a higher sarcopenia prevalence than controls and patients with CKD stages 1 and 2 (all p < 0.05). CKD patients (stages 1 and 2) had elevated plasma zonulin and LBP when compared with CKD stages 4 and 5. Plasma zonulin and LBP exhibited significant correlations with renal function, HGS, gait speed, SPPB scores, and oxidative stress markers in CKD stages 4 and 5 (all p < 0.05). However, similar relations were not found in early CKD. Collectively, intestinal leak may be contributing to sarcopenia and physical disability in the advanced stages of CKD.
Asunto(s)
Insuficiencia Renal Crónica , Sarcopenia , Humanos , Masculino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/sangre , Sarcopenia/sangre , Sarcopenia/fisiopatología , Sarcopenia/epidemiología , Anciano , Persona de Mediana Edad , Biomarcadores/sangre , Fuerza de la Mano/fisiología , Haptoglobinas , Precursores de Proteínas/sangreRESUMEN
Chronic obstructive pulmonary disease (COPD) is frequently associated with age-related muscle loss or sarcopenia. However, the exact molecular mechanism of muscle loss in COPD remains elusive. We investigated the association of chronic dysregulation of sarcoplasmic reticulum (SR) protein homeostasis (a condition called SR stress) and myonuclear disorganization with sarcopenia in patients with COPD. Markers of SR stress and their downstream consequences, including apoptosis and inflammation, were upregulated in patients with COPD. The maximal SR Ca2+ ATPase (SERCA) activity was significantly reduced in advanced COPD as compared to healthy controls. Single muscle fiber diameter and cytoplasmic domain per myonucleus were significantly smaller in patients with advanced COPD than in healthy controls. Increased disruption of myonuclear organization was found in the COPD patients as compared to healthy controls. These changes in SR dysfunction were accompanied by elevated global levels of oxidative stress, including lipid peroxidation and mitochondrial reactive oxygen species (ROS) production. Altogether, our data suggest that muscle weakness in advanced COPD is in part associated with the disruption of SR protein and calcium homeostasis and their pathological consequences.
Asunto(s)
Enfermedades Pulmonares , Sarcopenia , Calcio/metabolismo , Humanos , Enfermedades Pulmonares/metabolismo , Estrés Oxidativo , Sarcopenia/metabolismo , Retículo Sarcoplasmático/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismoRESUMEN
PURPOSE: Sarcopenia or age-related muscle loss is a common finding in patients with chronic obstructive pulmonary disease (COPD) and may lead to functional compromise. The contribution of an increased gut permeability to muscle decline in COPD may be of primary relevance. We measured the plasma zonulin levels (a marker of intestinal permeability) as potential predictors of sarcopenia in COPD patients during pulmonary rehabilitation (PR). METHOD: We recruited male, 56-73 years healthy controls and patients with COPD (N = 70-76/group) to measure plasma zonulin, handgrip strength (HGS), body composition and biochemical parameters. All measurements were performed before and one year following the PR. RESULTS: COPD patients had elevated plasma zonulin levels at baseline (22.8% higher vs healthy controls, p < 0.05), which were partially reduced (12.1% reduction vs baseline, p < 0.05) with PR. PR also resulted in improved HGS (8.5% increase, p < 0.05) as well as plasma c-reactive protein (CRP) (11.1% reduction, p < 0.05) and 8-isoprostanes (22.1% reduction, p < 0.05) as markers of inflammation and oxidative stress, respectively. Simple regression analysis revealed dynamic correlations of the alterations in zonulin levels with HGS, CRP and 8-isoprostanes during PR (all p < 0.05). These changes were associated with a reduction in sarcopenia incidence following PR. CONCLUSION: Altogether, increased intestinal permeability may contribute to muscle decline in COPD, which is partially restored by PR. Plasma zonulin may be a useful marker to evaluate sarcopenia phenotype in COPD.