Normal Fat-free Mass Research Articles

Smoke-induced neuromuscular junction degeneration precedes the fibre type shift and atrophy in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is largely caused by smoking, and patient limb muscle exhibits a fast fibre shift and atrophy. We show that this fast fibre shift is associated with type grouping, suggesting recurring cycles of denervation-reinnervation underlie the type shift. Compared to patients with normal fat-free mass index (FFMI), patients with low FFMI exhibited an exacerbated fibre type shift, marked accumulation of very small persistently denervated muscle fibres, and a blunted denervation-responsive transcript profile, suggesting failed denervation precipitates muscle atrophy in patients with low FFMI. Sixteen weeks of passive tobacco smoke exposure in mice caused neuromuscular junction degeneration, consistent with a key role for smoke exposure in initiating denervation in COPD. A neurological basis for the fast fibre shift and atrophy seen in limb muscle of patients with chronic obstructive pulmonary disease (COPD) has not been considered previously. The objective of our study was: (1) to determine if denervation contributes to fast fibre shift and muscle atrophy in COPD; and (2) to assess using a preclinical smoking mouse model whether chronic tobacco smoke (TS) exposure could initiate denervation by causing neuromuscular junction (NMJ) degeneration. Vastus lateralis muscle biopsies were obtained from severe COPD patients [n=10 with low fat-free mass index (FFMI), 65years; n=15 normal FFMI, 65years) and healthy age- and activity-matched non-smoker control subjects (CON; n=11, 67years), to evaluate morphological and transcriptional markers of denervation. To evaluate the potential for chronic TS exposure to initiate these changes, we examined NMJ morphology in male adult mice following 16weeks of passive TS exposure. We observed a high proportion of grouped fast fibres and a denervation transcript profile in COPD patients, suggesting that motor unit remodelling drives the fast fibre type shift in COPD patient limb muscle. A further exacerbation of fast fibre grouping in patients with low FFMI, coupled with blunted reinnervation signals, accumulation of very small non-specific esterase hyperactive fibres and neural cell adhesion molecule-positive type I and type II fibres, suggests denervation-induced exhaustion of reinnervation contributes to muscle atrophy in COPD. Evidence from a smoking mouse model showed significant NMJ degeneration, suggesting that recurring denervation in COPD is probably caused by decades of chronic TS exposure.

2D-DIGE proteomic analysis of vastus lateralis from COPD patients with low and normal fat free mass index and healthy controls

BackgroundChronic obstructive pulmonary disease (COPD) is associated with several extra-pulmonary effects of which skeletal muscle wasting is one of the most common and contributes to reduced quality of life, increased morbidity and mortality. The molecular mechanisms leading to muscle wasting are not fully understood. Proteomic analysis of human skeletal muscle is a useful approach for gaining insight into the molecular basis for normal and pathophysiological conditions.MethodsTo identify proteins involved in the process of muscle wasting in COPD, we searched differentially expressed proteins in the vastus lateralis of COPD patients with low fat free mass index (FFMI), as a surrogate of muscle mass (COPDL,n = 10) (FEV1 33 ± 4.3% predicted, FFMI 15 ± 0.2 Kg.m−2), in comparison to patients with COPD and normal FFMI (COPDN,n = 8) and a group of age, smoking history, and sex matched healthy controls (C, n = 9) using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) technology, combined with mass spectrometry (MS). The effect of silencing DOT1L protein expression on markers of cell arrest was analyzed in skeletal muscle satellite cells (HSkMSCs) in vitro and assessed by qPCR and Western blotting.ResultsA subset of 7 proteins was differentially expressed in COPDL compared to both COPDN and C. We found an increased expression of proteins associated with muscle homeostasis and protection against oxidative stress, and a decreased expression of structural muscle proteins and proteins involved in myofibrillogenesis, cell proliferation, cell cycle arrest and energy production. Among these was a decreased expression of the histone methyltransferase DOT1L. In addition, silencing of the DOT1L gene in human skeletal muscle satellite cells in vitro was significantly related to up regulation of p21 WAF1/Cip1/CDKN1A, a marker of cell arrest and ageing.Conclusions2D-DIGE coupled with MS identified differences in the expression of several proteins in the wasted vastus lateralis that are relevant to the disease process. Down regulation of DOT1L in the vastus lateralis of COPDL patients may mediate the muscle wasting process through up regulation of markers of cell arrest and senescence.

Eating Behaviors, Body Composition and Risk of Relapse among Persons withdrawing from Substance Abuse: A 3-months Follow-up Study

Objective: To describe eating behaviors and body composition before, during and after substance abuse withdrawal, and to assess if these factors were related with withdrawal outcome. Methods: This was a three month follow-up study examining eating behaviors (measured by validated questionnaires and interview), substance use (assessed with Addiction Severity Index) anthropometry (weight, height and bioimpedance for body composition), medical conditions and psycho-social environment (recorded from medical files and Addiction Severity Index) of 117 patients enrolling in a detoxification program at the University Hospitals, Geneva, Switzerland. Characteristics at baseline and after one month were compared according to patients’ outcome. Variables showing a significant association with relapse were entered in a multivariate logistic regression Results: Most patients were men (84, 71%), and detoxified from alcohol (95, 81%). Relapse rates were 27% after 1 month and 45% after 3 months. Eating disorders were rare but 19% scored high on shape concern scale, 35% experienced nibbling, 20% compulsive night eating and 14% binge episodes, 24% displayed lower than normal fat-free mass and 40% had higher than normal fat mass. Bivariate analysis showed that low nutritional status (low BMI, or low fat mass or low fat free mass), was associated with a decreased risk of relapse. Withdrawal from drugs, higher tobacco consumption and higher severity index for legal area were associated with relapse. These determinants showed no effect on outcome in a multivariate analysis. Conclusion: Problematic eating behaviors were common in this group, whereas eating disorders were rare. Relapse rate was high. No variable was related with relapse at multivariate level. As in general population, overweight and high fat mass were common among persons abusing substances. BMI was a poor indicator of their nutritional status. Our study suggests attention should be given to patients’ eating behaviors, weight and shape preoccupation during substance withdrawal and follow-up.

Cardiometabolic risk in overweight subjects with or without relative fat-free mass deficiency: The Strong Heart Study

Background and aimSarcopenia is a condition mainly due to loss of fat-free mass (FFM) in elderly individuals. RFFMD, however, is also frequent in obese subjects due to abnormal body composition. Objective of this study was to evaluate the impact of relative fat-free mass deficiency (RFFMD) on cardiometabolic (CM) risk in obese normoglycemic individuals. Methods and resultsOverweight/obese American Indians from the Strong Heart Study population, without diabetes and with FBG ≤110 mg/dL and with GFR >60 mg/mL/1.73 m2 were selected for this analysis (n = 742). RFFMD was defined on the basis of a multivariable equation previously reported. Fasting glucose and 2 h-OGTT were measured together with urine albumin/creatinine excretion, laboratory and anthropometric parameters. In addition to lower FFM and greater adipose mass, participants with RFFMD had higher body mass index, waist circumference, C-reactive protein, fibrinogen, insulin resistance and urinary albumin/creatinine than participants with normal FFM (all p < 0.001); they also had a greater prevalence of hypertension, impaired glucose tolerance (IGT) or OGTT-diabetes than participants with normal FFM (all p < 0.003) and a near 2-fold greater probability of significant proteinuria (p < 0.01). RFFMD was more frequent in women than in men: significant sex-RFFMD interactions were found for BMI and waist circumference (both p < 0.0001). ConclusionsRFFMD in overweight/obese normoglycemic individuals is associated with greater probability of hypertension, abnormalities of glucose tolerance and proteinuria. Assessment of RFFRMD might, therefore, help stratifying cardiometabolic risk among normoglycemic individuals with overweight/obesity.

Évaluation de l’état nutritionnel et de la composition corporelle du patient BPCO : comparaison de plusieurs méthodes

In chronic obstructive pulmonary disease (COPD), loss of fat-free mass (FFM) reduces the prognosis. To assess their nutritional status and compare the relevance of several nutritional criteria, 47 COPD patients, already enrolled in our pulmonary rehabilitation programme, were evaluated. Assessment of nutritional status included anthropometry, serum albumin and transthyretin, bioimpedance analysis (BIA) and 3-day dietary record. The accuracy of these nutritional parameters was determined by comparison with FFM measured by BIA. The agreement between BIA and the 4-skinfold-thickness method was determined by statistical correlation and the Bland and Altman method. Energy intake, health care requirements and quality of life (QOL) score were compared with the FFM. According to the criteria used, the prevalence of undernutrition varied between 4 and 49%. In comparison with BIA, body mass index (BMI) below 20, triceps skinfold below the 5th percentile and transthyretin below 0.20 g/L had a specificity of around 100% for the diagnosis of undernutrition. There was a good agreement between BIA and the 4-skinfold-thickness method for the assessment of FFM (r=0.86, P<0.0001). Prior to any nutritional intervention, the patients with low FFM had higher protein-energy intake than patients with normal FFM. Low FFM was associated with a greater number of visits to the doctor, but had no impact on QOL. The assessment of FFM by BIA is the most sensitive method to detect undernutrition in COPD patients. Lowered values of BMI, triceps skinfold and transthyretin are predictive of loss of FFM.

The influence of body composition on respiratory muscle, lung function and diaphragm thickness in adults with cystic fibrosis

Background: Weight loss and loss of fat-free mass (FFM) are associated with peripheral muscle wasting in cystic fibrosis (CF) although whether this co-exists with loss of diaphragm mass remains unclear. Methods: FFM was determined by dual-energy X-ray absorptiometry and bioelectrical impedance in 40 adults with CF and 30 age-matched healthy subjects (HS). Diaphragm thickness at functional residual capacity (FRC) [TDIrel] and total lung capacity (TLC) [TDIcont] and thickening ratio (TR) were assessed by ultrasonography. Inspiratory muscle strength and work capacity were determined by maximal inspiratory pressure (PImax), and sustained PImax (SPImax); pulmonary function (RV, VC and TLC) and physical activity status (PAS) were also determined. Results: When the CF patients were assessed as a group (low and normal FFM) they had similar age, weight, height and PAS compared to the HS, although patients had lower FFM ( p < 0.05), VC and TLC than the HS ( p < 0.01). In addition, although PImax, TDIrel, TDIcont and TR were similar between the patients and the HS, SPImax was lower in the patients ( p < 0.01). When analyses were made between patients with low versus normal FFM and between patients with low FFM and HS no significant differences were found between overall weight although TDIrel, TDIcont, TR and PAS were all reduced in patients with low FFM ( p < 0.01). Conclusions: PImax is relatively well preserved in adults with CF although there is a relationship between the loss of inspiratory muscle work capacity, FFM, PAS and pulmonary function. Furthermore loss of FFM is associated with loss of diaphragm muscle mass.

Cellular proteolysis and systemic inflammation during exacerbation in cystic fibrosis

Background Weight loss indicates a poor prognosis in cystic fibrosis (CF). We hypothesised that fat-free mass (FFM) depletion and increased systemic inflammation would be associated with increased cellular proteolysis during an exacerbation of the respiratory symptoms. Patients were studied prospectively from the beginning of treatment with antibiotics when admitted to the Adults CF Centre. Methods Twenty six patients with CF were studied at the start and end of antibiotic treatment and 2 weeks later. Mean (95% CI) FEV 1 when clinically stable was 54.1 (44.5, 62.6)% predicted. Urinary excretion of Pseudouridine (5-ribosyluracil, PSU) was determined as an indicator of cellular protein breakdown. Body composition was assessed by dual energy X-ray absorptiometry (DXA). Results Patients had increased concentrations of PSU at all assessments ( p<0.01). Those with a low FFM had greater PSU (ratio to FFMI) than those with a normal FFM at all assessments. At the start of treatment, PSU was related to FFM, C-reactive protein (CRP) ( p<0.05) and tumour necrosis factor (TNF)α soluble receptors (sr) I and II ( p<0.01). Circulating inflammatory mediators were greater in patients than in healthy subjects at all assessments. Conclusion Increased protein breakdown is associated with a low FFM and increased systemic inflammation and it may be a contributory mechanism of poor weight preservation in CF.

Hidden Depletion of Fat-Free Mass and Bone Mineral Density in Adults With Cystic Fibrosis

Weight loss is associated with reduced survival in patients with cystic fibrosis (CF). We hypothesized that some adult patients with a normal body mass index (BMI) have evidence of hidden fat-free mass (FFM) and bone mineral density (BMD) depletion that is linked to more severe disease. Fat mass (FM), FFM, and BMD were determined by dual-energy x-ray absorptiometry (DXA) and by bioelectric impedance in 56 adults in clinically stable condition and 20 age-matched healthy subjects. FM index and FFM index (FFMI) [kilograms per meter squared] of the right arm, leg, and trunk (ratio to height squared) were calculated. Lung function, including the maximum inspiratory pressure (MIP) and sustained MIP (SMIP), physical activity, serum C-reactive protein (CRP) and the number of exacerbations in the previous year were recorded. Patients had a lower total FFM than healthy subjects (p < 0.01), while FM was similar. Of the 56 patients, 30 patients had a normal BMI, of which 12 patients had a low FFM (hidden loss) by DXA. The right arm, leg, and trunk FFMI and BMD at hip sites were less in these patients than in those with a normal BMI and normal FFM (all p < 0.01). This group had a lower FEV(1), SMIP, more frequent exacerbations, and greater circulating CRP (all p < 0.05). In adults with CF, apparent or hidden loss of FFM, rather than weight loss, was related to overall disease severity. Hidden depletion of FFM was associated with increased loss of BMD and systemic inflammatory activity.

Muscle Strength and Exercise Kinetics in COPD Patients with a Normal Fat-Free Mass Index Are Comparable to Control Subjects.

Muscle Strength and Exercise Kinetics in COPD Patients with a Normal Fat-Free Mass Index Are Comparable to Control Subjects.

Muscle Strength and Exercise Kinetics in COPD Patients With a Normal Fat-Free Mass Index Are Comparable to Control Subjects

This study was designed to investigate the extent of clinical muscle dysfunction in stable patients with COPD who were attending an out-patient pulmonary clinic compared with that of age-matched control subjects without COPD. Respiratory muscle and hand grip strength, steady-state O(2) kinetics, and body composition were measured in 32 patients with COPD (19 women) [mean (+/- SD) FEV(1), 38 +/- 11% predicted] and 36 age-matched control subjects (13 women). Measurements of handgrip force (mean, 97 +/- 32% vs 106 +/- 26% predicted, respectively), maximal expiratory pressure (mean, 57 +/- 33% vs 61 +/- 22% predicted, respectively), steady-state O(2) kinetics (mean tau, 72 +/- 34 s vs 78 +/- 37 s, respectively) and steady-state CO(2) kinetics (mean tau, 77 +/- 38 s vs 65 +/- 32 s, respectively) at submaximal exercise were similar in patients and control subjects. All the subjects, except for one female COPD patient, had a normal fat-free mass index (FFMI), although on average the FFMI was lower in male patients (19.8 +/- 2.8) than in male control subjects (23.0 +/- 2.8; p < 0.01). In patients with COPD who were attending a regular outpatient pulmonary clinic, there was no evidence of reduced upper extremity and expiratory muscle strength or prolonged O(2) and CO(2) kinetics during isowork submaximal cardiopulmonary exercise compared to healthy, age-matched control subjects. Also, a normal body composition was found in nearly all COPD patients. This argues against the existence of a clinically significant systemic myopathy in most stable patients with severe COPD and normal FFMI.

Bone Density, Body Composition, and Inflammatory Status in Cystic Fibrosis

Low body weight and loss of bone mass are major problems in adults with cystic fibrosis (CF) and chronic pulmonary infection. Although these complications probably have a multifactorial origin, we hypothesized that the continuous acute-phase inflammatory and catabolic state may contribute. We determined body composition, bone turnover, physical activity, and circulating interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and their soluble receptors in 22 adults with CF and 22 age- and sex-matched healthy subjects. Comparisons were also made within patients before and after treatment of an exacerbation of respiratory symptoms. The patients had a lower mean (95% confidence interval [CI]) fat-free mass (FFM) 39.9 (36.3, 43.6) kg than healthy subjects, 49.4 (45.1, 53.7) kg, p < 0.05. The patients were in negative nitrogen balance and 20 had bone mineral density (BMD) Z scores </= 2.5 SD (n = 13) or </= 1 SD (n = 7) at least at one site. They had increased bone collagen breakdown, greatest in those with a reduced FFM. BMD was related to FEV(1) (r = 0.44), IL-6 (r = -0.60), and TNF-alpha-soluble receptors (r = -0.42, r = -0.50). Patients with a low FFM had greater concentrations of IL-6, which suppressed less after antibiotic treatment than in those with a normal FFM. Those with a low FFM were more catabolic and less active than those with a normal FFM. The association between altered body composition, catabolic status, and circulating inflammatory mediators suggests that chronic pulmonary infection in adults with CF may be a contributory factor in the long-term complications of low weight and bone disease.