RESUMEN
Oxidative/carbonyl stress is elevated in lower-limb muscles of patients with chronic obstructive pulmonary disease (COPD). Carnosine is a skeletal muscle antioxidant particularly present in fast-twitch fibers. The aims of the present study were to compare muscle carnosine, oxidative/carbonyl stress, antioxidants, and fiber characteristics between patients with COPD and healthy controls (HCs) and between patients after stratification for airflow limitation (mild/moderate vs. severe/very severe), as well as to investigate correlates of carnosine in patients with COPD. A vastus lateralis muscle biopsy was obtained from 40 patients with stable COPD and 20 age- and sex-matched HCs. Carnosine, oxidative/carbonyl stress, antioxidants, fiber characteristics, quadriceps strength and endurance (QE), VÌo2peak (incremental cycle test), and physical activity (PA) were determined. Patients with COPD had a similar carnosine concentration [4.16 mmol/kg wet weight (WW; SD = 1.93)] to HCs [4.64 mmol/kg WW (SD = 1.71)] and significantly higher percentage of fast-twitch fibers and lower QE, VÌo2peak, and PA versus HCs. Patients with severe/very severe COPD had a 31% lower carnosine concentration [3.24 mmol/kg WW (SD = 1.79); n = 15] versus patients with mild/moderate COPD [4.71 mmol/kg WW (SD = 1.83); n = 25; P = 0.02] and significantly lower VÌo2peak and PA versus patients with mild/moderate COPD. Carnosine correlated significantly with QE (rs = 0.427), VÌo2peak (rs = 0.334), PA (rs = 0.379), and lung function parameters in patients with COPD. In conclusion, despite having the highest proportion of fast-twitch fibers, patients with severe/very severe COPD displayed a 31% lower muscle carnosine concentration compared with patients with mild/moderate COPD. As no other markers of oxidative/carbonyl stress or antioxidants were affected, the observed carnosine deficiency is thought to be a possible first sign of muscle redox balance abnormalities.NEW & NOTEWORTHY Carnosine, particularly present in fast-twitch fibers, was investigated in the quadriceps of patients with chronic obstructive pulmonary disease (COPD). Carnosine concentration was similar between patients with COPD and healthy controls but was 31% lower in patients with severe/very severe COPD, despite their high proportion of fast-twitch fibers, versus patients with mild/moderate COPD. As no other markers of oxidative/carbonyl stress or antioxidants were affected, the observed carnosine deficiency is thought to be a possible first sign of muscle redox balance abnormalities.
Asunto(s)
Carnosina , Enfermedad Pulmonar Obstructiva Crónica , Antioxidantes/metabolismo , Carnosina/metabolismo , Humanos , Fibras Musculares Esqueléticas , Músculo Esquelético/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Músculo Cuádriceps/metabolismoRESUMEN
Obesity is associated with a disturbed adipose tissue (AT) function characterized by adipocyte hypertrophy, an impaired lipolysis and pro-inflammatory phenotype, which contributes to insulin resistance (IR). We investigated whether AT phenotype in different AT depots of obese individuals with and without type 2 diabetes mellitus (T2DM) is associated with whole-body IR. Subcutaneous (SC) and visceral (V) AT biopsies from 18 lean, 17 obese and 8 obese T2DM men were collected. AT phenotype was characterized by ex vivo measurement of basal and stimulated lipolysis (mature adipocytes), adipocyte size distribution (AT tissue sections) and AT immune cells (flow cytometry). In VAT, mean adipocyte size, CD45+ leukocytes and M1 macrophages were significantly increased in both obese groups compared to lean individuals. In SCAT, despite adipocyte hypertrophy, no significant differences in immune cell populations between groups were found. In SCAT, multiple linear regression analysis showed that none of the AT phenotype markers independently contributed to HOMA-IR while in VAT, mean adipocyte size was significantly related to HOMA-IR. In conclusion, beside adipocyte hypertrophy in VAT, M1 macrophage- or B-cell-mediated inflammation, may contribute to IR, while inflammation in hypertrophic SCAT does not seem to play a major role in IR.
Asunto(s)
Diabetes Mellitus Tipo 2/inmunología , Grasa Intraabdominal/patología , Obesidad/inmunología , Grasa Subcutánea/patología , Adipocitos , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/patología , Humanos , Resistencia a la Insulina , Grasa Intraabdominal/citología , Grasa Intraabdominal/inmunología , Antígenos Comunes de Leucocito/metabolismo , Modelos Lineales , Lipólisis , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/patología , Fenotipo , Grasa Subcutánea/citología , Grasa Subcutánea/inmunologíaRESUMEN
Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in human substrate and energy metabolism, thereby connecting the heart with several insulin-sensitive organs like adipose tissue, skeletal muscle and liver. Obesity may be associated with an impaired regulation of the natriuretic peptide system, also indicated as a natriuretic handicap. Evidence points towards a contribution of this natriuretic handicap to the development of obesity, type 2 diabetes mellitus and cardiometabolic complications, although the causal relationship is not fully understood. Nevertheless, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on current literature regarding the metabolic roles of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Furthermore, it will be discussed how exercise and lifestyle intervention may modulate the natriuretic peptide-related metabolic effects.
Asunto(s)
Resistencia a la Insulina , Metabolismo de los Lípidos , Péptidos Natriuréticos/sangre , Péptidos Natriuréticos/deficiencia , Adipoquinas/sangre , Diabetes Mellitus Tipo 2/sangre , Ejercicio Físico , Humanos , Estilo de Vida , Hígado/metabolismo , Músculo Esquelético/metabolismo , Péptidos Natriuréticos/metabolismo , Obesidad/sangre , Receptores del Factor Natriurético AtrialRESUMEN
The impact of high-intensity exercise on disease progression and muscle contractile properties in experimental autoimmune encephalomyelitis (EAE) remains unclear. Control (CON) and EAE rats were divided into sedentary and exercise groups. Before onset (experiment 1, n=40) and after hindquarter paralysis (experiment 2, n=40), isokinetic foot extensor strength, cross sectional area (CSA) of tibialis anterior (TA), extensor digitorum longus (EDL) and soleus (SOL) and brain-derived neurotrophic factor (BDNF) levels were assessed. EAE reduced muscle fiber CSA of TA, EDL and SOL. In general, exercise was not able to affect CSA, whereas it delayed hindquarter paralysis peak. CON muscle work peaked and declined, while it remained stable in EAE. BDNF-responses were not affected by EAE or exercise. In conclusion, EAE affected CSA-properties of TA, EDL and SOL, which could, partly, explain the absence of peak work during isokinetic muscle performance in EAE-animals. However, exercise was not able to prevent muscle fiber atrophy.
Asunto(s)
Encefalomielitis Autoinmune Experimental/patología , Fibras Musculares Esqueléticas/patología , Condicionamiento Físico Animal/fisiología , Animales , Peso Corporal , Factor Neurotrófico Derivado del Encéfalo/sangre , Progresión de la Enfermedad , Ingestión de Alimentos , Encefalomielitis Autoinmune Experimental/sangre , Encefalomielitis Autoinmune Experimental/fisiopatología , Femenino , Fibras Musculares Esqueléticas/fisiología , Fuerza Muscular , Distribución Aleatoria , Ratas Endogámicas LewRESUMEN
BACKGROUND: Patients with MS (pwMS) often experience resting ventilatory anomalies. Ventilatory function during exercise and impact of long-term training intervention remains however uncertain. AIM: The aim of this study was to examine the ventilatory function during exercise and impact of a 6-month training intervention in pwMS. DESIGN: Combination of a cross-sectional (part 1) and randomized controlled trial (part 2). SETTING: University rehabilitation facility. POPULATION: Caucasian patients with MS and healthy controls. METHODS: In part 1, the ventilatory function during submaximal endurance exercise was compared between pwMS (N.=37) and healthy participants (N.=15). In part 2, pwMS were then randomly assigned to a 6-month training intervention (N.=16) or usual care (N.=11). Following training intervention, ventilatory function during exercise was re-evaluated. RESULTS: Despite comparable relative exercise testing intensities between groups in part 1, significantly elevated steady-state exercise dead space/tidal volume ratio, O2 uptake and CO2 output equivalent, end-tidal O2 pressure, ratings of perceived exertion and lowered end-tidal CO2 pressure and O2 pulse was observed in pwMS (P<0.05). The degree of ventilatory dysfunction during exercise correlated significantly with ratings of perceived exertion and blood lactate content (P<0.05). In part 2, despite an improved exercise tolerance (based on reductions in heart rate, blood lactate content and ratings of perceived exertion during exercise at similar workload) after a 6-month training intervention, ventilatory dysfunction remained present during endurance exercise (P>0.05). CONCLUSION: Patients with MS experience a ventilatory dysfunction during endurance exercise, which is related to worse exercise tolerance. This ventilatory anomaly remains present after long-term training intervention. CLINICAL REHABILITATION IMPACT: Patients with MS experience ventilatory dysfunction during exercise. This dysfunction is related to exercise tolerance and ratings of perceived exertion. Long-term exercise training did not remediate this ventilatory dysfunction. The systematic examination of the pulmonary/cardiovascular system at rest and during exercise is recommended in MS.