Normal Body Composition Research Articles

Clinical impact of body composition phenotypes in patients with COPD: a retrospective analysis.

Abnormal body composition is an independent determinant of COPD outcomes. To date, it is already known that patient stratification into body composition phenotypes are associated with important outcomes, such as exercise capacity and inflammation, but there are no data comparing physical activity and muscle strength among these phenotypes. Thus, the aim of this study was to compare clinical characteristics and physical function in patients with COPD stratified into body composition phenotypes. Two-hundred and seventy stable COPD patients were classified according to the 10th and 90th percentiles of sex-age-BMI-specific reference values for fat-free and fat mass indexes into four groups: Normal body composition (NBC), Obese, Sarcopenic, and Sarcopenic-obese (SO). Patients underwent assessment of exercise capacity, peripheral and respiratory muscle strength, physical activity, dyspnea severity, functional status, and symptoms of anxiety and depression. The prevalence of patients classified as NBC, Obese, Sarcopenic, and SO was 39%, 13%, 21%, or 27%, respectively. SO presented lower 6MWT compared with NBC (P < 0.05). Sarcopenic and SO groups presented worse muscle strength compared with NBC (P < 0.05). Sarcopenic group presented more time in moderate-to-vigorous physical activity compared to all other groups (P < 0.05) and less sedentary time when compared with NBC and obese groups (P < 0.05). There were no differences regarding dyspnea severity, functional status, and symptoms of anxiety and depression (P > 0.16). Sarcopenic and SO groups had, respectively, 7.8 [95% CI: 1.6-37.7] and 9.5 [2.2-41.7] times higher odds to have a 6MWT equal or lower to 350 meters. Body composition phenotypes are associated with physical function in patients with COPD. Sarcopenic-obese patients were the most impaired.

Physical activity in healthy urban adults and its association with body composition parameters

An adequate amount of physical activity (PA) in adults improves cardio-respiratory fitness, metabolic health and helps maintain a normal body weight and composition. Here we examined sex- and occupation-related PA patterns and their association with body composition parameters. Healthy volunteers (n = 97) aged 21–49 years completed a self-administered PA questionnaire and characterized their occupational duties depending on the volume of the physical work involved. A bio-impedance analyser was used to determine body composition. Men reported more metabolic equivalent of task (MET) minutes/week of vigorous PA than women (p &lt; 0.05). Participants with low occupational PA had less walking, moderate and total MET minutes/week, and more sitting time than those with moderate and vigorous occupational PA (p &lt; 0.05), but their body composition parameters did not differ. In males, negative correlations were found between body fat percentage, visceral fat range, segmental fat mass, and moderate MET minutes/week, whereas positive associations were observed between muscle mass in legs and vigorous MET minutes/week (p&lt;0.05). In females, negative correlations were found between visceral fat and vigorous MET minutes/week but positive – between lean body mass, trunk and leg muscle mass, and moderate PA (p &lt; 0.05). These observed associations might be used to develop interventions to promote sex- and occupation-specific PA.

Differences in micro-RNA expression profile between vastus lateralis samples and myotubes in COPD cachexia.

Quadriceps muscle weakness and wasting are common comorbidities in chronic obstructive pulmonary disease (COPD). Micro-RNA expression upregulation may favor muscle mass growth and differentiation. We hypothesized that the profile of muscle-enriched micro-RNAs in cultured myotubes differs between patients with COPD of a wide range of body composition and healthy controls and that expression levels of those micro-RNAs from patients with COPD and controls differ between in vivo and in vitro conditions. Twenty-nine patients with COPD [ n = 15 with muscle wasting and fat-free mass index (FFMI) 15 kg/m2 and n = 14 with normal body composition and FFMI 18 kg/m2] and 10 healthy controls (FFMI 19 kg/m2) were consecutively recruited. Biopsies from the vastus lateralis muscle were obtained in all study subjects. A fragment of each biopsy was used to obtain primary cultures, in which muscle cells were first proliferated to be then differentiated into actual myotubes. In both sets of experiments (in vivo biopsies and in vitro myotubes) the following muscle-enriched micro-RNAs from all the study subjects were analyzed using quantitative real-time PCR amplification: micro-RNA (miR)-1, miR-133a, miR-206, miR-486, miR-29b, miR-27a, and miR-181a. Whereas the expression of miR-1, miR-206, miR-486, and miR-29b was upregulated in the muscle biopsies of patients with COPD compared with those of healthy controls, levels of none of the studied micro-RNAs in the myotubes (primary cultured cells) significantly differed between patients with COPD and the controls. We conclude from these findings that environmental factors (blood flow, muscle metabolism, and inflammation) taking place in vivo (biopsies) in muscles may account for the differences observed in micro-RNA expression between patients with COPD and controls. In the myotubes, however, the expression of the same micro-RNAs did not differ between the study subjects as such environmental factors were not present. These findings suggest that therapeutic strategies should rather target environmental factors in COPD muscle wasting as the profile of micro-RNA expression in myotubes was similar in patients to that observed in the healthy controls. NEW & NOTEWORTHY Environmental factors taking place in vivo (biopsies) in the muscles may explain differences observed in micro-RNA expression between patients with chronic obstructive pulmonary disease (COPD) and controls. In the myotubes, however, the expression of the same micro-RNAs did not differ between the study subjects as such environmental factors were not present. These findings suggest that therapeutic strategies should rather target environmental factors in COPD muscle wasting and cachexia as micro-RNA expression profile in myotubes was similar between patients and controls.

Muscle Depletion Is an Important and Clinically Relevant Predictor of Outcomes after Autologous Hematopoietic Cell Transplantation

▪Introduction: High intensity treatments such as autologous hematopoietic cell transplantation (HCT) can be curative for patients with relapsed/refractory lymphoma (Hodgkin [HL], non-Hodgkin [NHL]), but this needs to be balanced by the risk of non-relapse mortality (NRM) associated with HCT and potentially sub-optimal disease response with less intensive treatments. Measures of pre-treatment body composition such as quantity and quality of muscle are prognostic in patients with solid tumors, but their association with post-HCT outcomes is unknown. We examined the prognostic significance of muscle depletion prior to HCT, defined by having both low muscle quantity (lumbar skeletal muscle index [SMI]) and quality (muscle attenuation [MA]) on computed tomography (CT) imaging, in a population-based cohort of patients undergoing autologous HCT for lymphoma. Next, we examined the prognostic significance of muscle depletion after HCT in a subset of patients with normal muscle composition prior to HCT, allowing us to examine the impact of change in body composition over time.Methods: 440 consecutive patients with lymphoma, age ≥18y, who underwent a first HCT between 2009 and 2014 at a single institution were included in the study. Measures of muscle quantity (SMI) and quality (MA) were ascertained from pre- and post-HCT abdominal CT scans using image analysis software (SliceOmatic; Tomovision, Quebec, Canada). SMI was calculated as the ratio of skeletal muscle area (cm2) divided by height (m)2. Sex and body mass index (BMI)-specific cutoff values of low SMI and MA were used to identify patients with muscle depletion (J Clin Oncol 2013 31:1539). Measurements were made by trained researchers blinded to patient demographics and HCT outcome (Figure 1); 3rd lumbar vertebra was used as a landmark because of its high correlation with whole-body muscle mass (J Clin Oncol 2016 34:1339). This report is limited to 321 (73%) patients with CT scans performed ≤90 days from HCT. Cumulative incidence of NRM was calculated taking into consideration competing risk of disease-related mortality. Kaplan-Meier method was used to examine overall survival (OS). Multivariable Cox regression analysis was used to calculate the hazard ratio (HR) estimates and 95% confidence intervals (CI), adjusted for relevant covariates (demographics, diagnosis, pre-HCT Karnofsky performance score [KPS] and comorbidity index [HCT-CI]).Results: Sixty-two (19.3%) patients had muscle depletion pre-HCT. Median age at HCT was 53y (range: 18-78); 62.0% were male; 54.0% were non-Hispanic white; Diagnoses: HL (N=84 [26.2%]), NHL (N=237 [73.8%]); KPS ≤80 (N=87 [27.1%]); HCT-CI ≥3 (N=52 [16.2%]). Impact of pre-HCT muscle depletion: Patients with pre-HCT muscle depletion had significantly worse 5-y OS (56.4% vs. 77.8%, p<0.001; Figure 2) and higher NRM (11.4% vs. 5.1%, p=0.05) when compared to those with normal body composition. OS was especially poor for patients who were obese (BMI ≥30 kg/m2) and had muscle depletion (20.0% vs. 77.1%, p<0.001) pre-HCT. Median length of hospitalization was also significantly longer (27d vs. 23d; p=0.03) among patients with muscle depletion. Muscle depletion was associated with a 2.2-fold (HR=2.2 [CI: 1.0-4.5]) risk of NRM and 1.8-fold (HR=1.8 [CI: 1.1-3.1]) risk of all-cause mortality when compared to those with normal body composition. Impact of post-HCT muscle depletion: Among 223 patients with normal body composition prior to HCT, 24 (9.3%) developed muscle depletion after HCT, detected at a median 63d (range 27-165) from HCT. In these patients, there was a 3-fold (HR=3.1 [CI: 1.5-6.4]) risk of all-cause mortality compared to those who maintained normal muscle composition throughout HCT.Conclusion: Muscle depletion is an important and independent predictor of outcomes after HCT, with potential additional downstream impacts on health-economic outcomes such as length of hospitalization and the burden of chronic morbidity in long-term survivors. Taken together, these data form the basis for real-time decision making prior to HCT (e.g. pre-habilitation, less intensive treatment approaches), or during HCT (e.g. dietary optimization, increased supportive care services, resistance training), setting the stage for innovative strategies to improve outcomes after HCT. DisclosuresChen:Affimed: Research Funding; Merck & Co., Inc.: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech Inc.: Consultancy; Millennium Pharmaceuticals: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Forman:Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.

Skeletal Muscle Parvin Regulates Exercise Tolerance and Glucose Homeostasis in Mice

Integrins are a family of cell surface receptors that bind to the extracellular matrix (ECM). ECM‐integrin connections are necessary for skeletal muscle (SkM) contractile function, but also contribute to diet‐induced insulin resistance (IR). Parvins are key proteins in the integrin signaling pathway, with α‐parvin being the most highly expressed in SkM. α‐parvin is a critical regulator of cytoskeletal dynamics needed for organelle and protein function and localization within the cell; however, its function in SkM in vivo has not been previously explored. In these studies, we tested the hypothesis that SkM α‐parvin is a requisite component of the ECM‐integrin signaling that regulates exercise tolerance and glucose homeostasis.SkM‐specific α‐parvin knockout mice (mPar‐KO) were generated using α‐parvin floxed mice and mice expressing Cre recombinase on the human α‐skeletal actin (HSA) promoter. Studies were performed on littermate α‐parvin flox/flox mice with (KO) or without (WT) Cre recombinase. Fasting blood glucose was measured at 6 weeks of age in chow‐fed mice. At 12 weeks of age, oral glucose tolerance testing (2 g/kg bodyweight) was performed on 5‐hr fasted chow or 6‐week high fat diet (HFD; 60% calories from fat) fed mice. Whole body indirect calorimetry and contextual behavior mapping of lean and HFD‐fed mice was performed at 18 weeks of age in a Promethion Metabolic Analyzer. In a cohort of 18‐week old chow‐fed mice, forced exercise performance was assessed using a graded treadmill stress test and voluntary wheel running (VWR) distance and efficiency (kcal/m traveled) were measured during indirect calorimetry experiments.6‐week old mPar‐KO mice had normal body composition but fasting hyperglycemia compared to WT littermates (n=15/group). 12‐week old chow‐fed mPar‐KO mice were glucose intolerant despite normal fasting glucose (n=5/group). No differences in fasting glucose or glucose tolerance were observed in HF‐fed WT or mPar‐KO mice (n=16–18/group). Forced exercise performance was reduced in mPar‐KO mice. Furthermore, VWR distance was ~80% lower in mPar‐KO mice (n=7–9/group). mPar‐KO mice also had an increased metabolic cost of exercise during VWR that was accompanied by longer bouts of off‐wheel roaming. mPar‐KO mice with a running wheel had an elevated respiratory quotient at rest, indicating increased fat utilization. HFD‐fed mPar‐KO mice had no differences in metabolism or activity compared to WT littermates.These data demonstrate that loss of SkM α‐parvin impairs exercise tolerance and elicits an increase in resting whole body reliance on fatty acids. In contrast to previous studies showing that SkM integrins contribute to diet‐induced IR, these data demonstrate that SkM α‐parvin is necessary for maintaining normal glucose homeostasis in chow‐fed mice and does not contribute to HFD‐induced IR. Collectively, these experiments suggest that SkM α‐parvin is a point of divergence for the beneficial effects of ECM‐integrin connections on exercise and deleterious effects on glucose homeostasis.Support or Funding InformationD.S.L. (AHA 16POST29910001); D.H.W. (NIH DK054902, DK059637 and DK076169).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Incomplete total body protein recovery in adolescent patients with anorexia nervosa

Bone health and growth during adolescence require adequate total body protein (TBPr). Renutrition for patients with anorexia nervosa (AN) should aim to normalize body composition and to recover both fat mass and TBPr. We intended to analyze predictors of protein status, including exercise status, in adolescents with AN and to investigate whether weight gain would replenish body protein deficits. We assessed TBPr in a longitudinal, observational study as height-adjusted nitrogen index (NI) using in vivo neutron activation analysis in 103 adolescents with AN [mean ± SD age, 15.6±1.4 y; body mass index (BMI, in kg/m2), 16.5±1.6] at the commencement of inpatient refeeding (T0), in 56 of these patients 7 mo thereafter as outpatients (T1), and in age-matched controls (C; n=51, 15.5±2.1 y, BMI 20.7±1.9). Lean tissue and fat mass were assessed by dual-energy X-ray absorptiometry. BMI, BMI standard deviation score, and lean tissue mass were tested as predictors of protein status using receiver operating characteristic analysis. At T0, NI was decreased in AN (AN, 0.88±0.10 compared with C, 1.00±0.08, P<0.001). In 34%, the patients showed protein depletion. Patients classified as ``exercisers'' had a higher NI than did ``nonexercisers'' (0.89 ± 0.11 compared with 0.85 ± 0.08, P = 0.045). BMI, BMI standard deviation score, and lean tissue mass did not show potential as predictors of protein status. Despite increases in weight (+6.9±4.5 kg), and BMI (+2.5±1.7), protein status did not improve (TBPr T0, 8.0±1.1 kg; T1, 8.1±1.0kg, P= 0.495). In an AN subgroup at 7 mo matched with controls in age (AN, 16.5±1.1y; C, 16.2±1.8 y) and BMI (AN, 20.5±1.4; C, 20.7±1.3), protein status was still not normalized in AN (NI: AN, 0.89±0.09 compared with C, 1.00±0.07, P < 0.001). Adolescents recovering from AN remained protein depleted at 7 mo after baseline assessment, even though they were weight restored.

Changes in maximal oxygen uptake during growth and development in girls who actively participate in basketball and in non-athletes girls: A longitudinal study

Background/Aim. It is well known that continuous engagement in physical activity is important for normal growth and development of children. Maximal oxygen uptake (VO2max), as a measure of functional state of the organism, is largely affected by level of physical activity, but it remains unclear to what extent it can be improved during childhood. The aim of the study was to evaluate dynamics of changes in aerobic capacity, anthropometric and body composition characteristics in active and non-active girls over a period of 3 years. Methods. A total of 48 young girls were included in the study. Girls were divided into 2 groups: training group consisted of 25 girls who played basketball (age 13.84 ? 0.94) and non-training group of 23 girls who were not involved in any organized sports (age 13.83 ? 0.98). Anthropometric and body composition characteristics were measured in order to monitor somatic growth during the study. VO2maxvalues were obtained by performing cardiopulmonary exercise testing on a treadmill. All parameters were measured every 6 months during 3-years period. Results. ANOVA analysis showed a significant time and group interaction effect on VO2max (p &lt; 0.001), body mass index (BMI) (p &lt; 0.001) and fat percentage (FAT%) (p &lt; 0.01). Also, there was an obvious increase in VO2max within both groups due to growth and development itself (p &lt; 0.001). Conclusion. The main finding of the study was an increase in VO2max due to growth and development. The girls who actively participated in basketball had higher level of aerobic capacity compared to non-active girls. Furthermore, continuous basketball training led to maintaining normal body composition in terms of FAT% and BMI, which altogether may imply that organized physical activity has a positive influence on evaluated characteristics.

FTO demethylase activity is essential for normal bone growth and bone mineralization in mice

The Fto gene locus has been linked to increased body weight and obesity in human population studies, but the role of the actual FTO protein in adiposity has remained controversial. Complete loss of FTO protein in mouse and of FTO function in human patients has multiple and variable effects. To determine which effects are due to the ability of FTO to demethylate mRNA, we genetically engineered a mouse with a catalytically inactive form of FTO. Our results demonstrate that FTO catalytic activity is not required for normal body composition although it is required for normal body size and viability. Strikingly, it is also essential for normal bone growth and mineralization, a previously unreported FTO function.

Body composition and clinical symptoms in patients with hip or knee osteoarthritis: Results from the KHOALA cohort.

To analyze the associations between body composition, notably low lean mass, and clinical symptoms [pain, physical function, quality of life (QoL)] in patients with symptomatic hip and/or knee OA. Cross-sectional study using data from the 3-year follow-up visit of the Knee and Hip OsteoArthritis Long-term assessment (KHOALA) cohort. Skeletal muscle and fat mass were measured by dual X-ray absorptiometry (DXA). Fat mass index (FMI) was defined as total fat mass/height2. Appendicular lean mass was adjusted on body mass index (ALM/BMI), and low lean mass was defined according to the definition of FNIH Sarcopenia Project recommendations. Pain and function were measured by the WOMAC index and QoL by the SF-36. In total, 358 patients underwent DXA (67% women, mean [SD] age 63.4 [8.4] years, mean BMI 29.5 [5.6]kg/m2). The visual analog scale (0-100) pain score was 38.0 [24.7] and 25.4% had hip and 74.6% knee OA. Low lean mass and ALM/BMI were associated with impaired QoL and WOMAC scores on bivariate analysis (all p ≤ 0.001) but not on multivariate analysis after adjustment for FMI. For patients with normal BMI, mean [SD] WOMAC scores were higher (greater impairment) with low lean mass than normal body composition (WOMAC function 33.4 [23.3] and 24.0 [17.4], p = 0.02), and mean SF-36 physical component score was lower (greater impairment) 40.3 [10.2] and (44.3 [8.4], p = 0.04). Among patients with obesity, low lean mass had no additional effect. For patients with OA and normal BMI, QoL and function were more impaired for those with than without low lean mass. Conserving muscle mass in people with OA could have functional and antalgic benefits especially for those with normal BMI.

NCB5OR Deficiency in the Cerebellum and Midbrain Leads to Dehydration and Alterations in Thirst Response, Fasted Feeding Behavior, and Voluntary Exercise in Mice

Cytosolic NADH-cytochrome-b5-oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues. We have previously reported that global ablation of NCB5OR in mice results in early-onset lean diabetes with decreased serum leptin levels and increased metabolic and feeding activities. The conditional deletion of NCB5OR in the mouse cerebellum and midbrain (conditional knock out, CKO mice) results in local iron dyshomeostasis and altered locomotor activity. It has been established that lesion to or removal of the cerebellum leads to changes in nutrient organization, visceral response, feeding behavior, and body weight. This study assessed whether loss of NCB5OR in the cerebellum and midbrain altered feeding or metabolic activity and had an effect on serum T3, cortisol, prolactin, and leptin levels. Metabolic cage data revealed that 16 week old male CKO mice had elevated respiratory quotients and decreased respiratory water expulsion, decreased voluntary exercise, and altered feeding and drinking behavior compared to wild-type littermate controls. Most notably, male CKO mice displayed higher consumption of food during refeeding after a 48-h fast. Echo MRI revealed normal body composition but decreased total water content and hydration ratios in CKO mice. Increased serum osmolality measurements confirmed the dehydration status of male CKO mice. Serum leptin levels were significantly elevated in male CKO mice while prolactin, T3, and cortisol levels remain unchanged relative to wild-type controls, consistent with elevated transcript levels for leptin receptors (short form) in the male CKO mouse cerebellum. Taken together, these findings suggest altered feeding response post starvation as a result of NCB5OR deficiency in the cerebellum.

Body composition in men with anorexia nervosa: Longitudinal study.

To compare body composition patterns before and after complete weight restoration in men with anorexia nervosa. Dual-energy X-ray absorptiometry (DXA) was used to measure body composition patterns in 10 men with anorexia nervosa before and after complete weight restoration, and in 10 healthy men matched to age and patients' post-treatment body mass index (BMI). Before weight restoration, men with anorexia nervosa displayed lower total body fat mass (FM) and lean mass (LBM) than those in the healthy comparison group, with a greater FM loss from the extremity than the trunk region. After short-term weight restoration, patients displayed complete normalization in total LBM and FM, but greater deposition of FM in the trunk region. Short-term weight restoration can normalize body composition patterns in men with anorexia nervosa, but results in a central adiposity phenotype. The clinical implication of this finding is unknown, but should be explored given the high levels of concern about central adiposity in anorexia nervosa.

Thyroid Function Variation in the Normal Range, Energy Expenditure, and Body Composition in L-T4-Treated Subjects.

It is not clear whether upper limits of the thyrotropin (TSH) reference range should be lowered. This debate can be better informed by investigation of whether variations in thyroid function within the reference range have clinical effects. Thyroid hormone plays a critical role in determining energy expenditure, body mass, and body composition, and therefore clinically relevant variations in these parameters may occur across the normal range of thyroid function. This was a cross-sectional study of 140 otherwise healthy hypothyroid subjects receiving chronic replacement therapy with levothyroxine (L-T4) who had TSH levels across the full span of the laboratory reference range (0.34 to 5.6 mU/L). Subjects underwent detailed tests of energy expenditure (total and resting energy expenditure, thermic effect of food, physical activity energy expenditure), substrate oxidation, diet intake, and body composition. Subjects with low-normal (≤2.5 mU/L) and high-normal (>2.5 mU/L) TSH levels did not differ in any of the outcome measures. However, across the entire group, serum free triiodothyronine (fT3) levels were directly correlated with resting energy expenditure, body mass index (BMI), body fat mass, and visceral fat mass, with clinically relevant variations in these outcomes. Variations in thyroid function within the laboratory reference range have clinically relevant correlations with resting energy expenditure, BMI, and body composition in L-T4-treated subjects. However, salutary effects of higher fT3 levels on energy expenditure may be counteracted by deleterious effects on body weight and composition. Further studies are needed before these outcomes should be used as a basis for altering L-T4 doses in L-T4-treated subjects.

Measurement of overweight and obesity an urban slum setting in sub-Saharan Africa: a comparison of four anthropometric indices.

BackgroundAs a result of both genetic and environmental factors, the body composition and topography of African populations are presumed to be different from western populations. Accordingly, globally accepted anthropometric markers may perform differently in African populations. In the era of rapid emergence of cardio-vascular diseases in sub-Saharan Africa, evidence about the performance of these markers in African settings is essential. The aim of this study was to investigate the inter-relationships among the four main anthropometric indices in measuring overweight and obesity in an urban poor African setting.MethodsData from a cardiovascular disease risk factor assessment study in urban slums of Nairobi were analyzed. In the major study, data were collected from 5190 study participants. We considered four anthropometric markers of overweight and obesity: Body Mass Index, Waist Circumference, Waist to Hip Ratio, and Waist to Height Ratio. Pairwise correlations and kappa statistics were used to assess the relationship and agreement among these markers, respectively. Discordances between the indices were also analyzed.ResultsThe weighted prevalence of above normal body composition was 21.6 % by body mass index, 28.9 % by waist circumference, 45.5 % by waist to hip ratio, and 38.9 % by waist to height ratio. The overall inter-index correlation was +0.44. Waist to hip ratio generally had lower correlation with the other anthropometric indices. High level of discordance exists between body mass index and waist to hip ratio. Combining the four indices shows that 791 (16.1 %) respondents had above normal body composition in all four indices. Waist circumference better predicted hypertension and hyperglycemia while waist to height ratio better predicted hypercholesterolemia.ConclusionsThere exists a moderate level of correlation and a remarkable level of discordance among the four anthropometric indices with regard to the ascertainment of abnormal body composition in an urban slum setting in Africa. Waist circumference is a better predictor of cardio-metabolic risk.

Sarcopenia, Obesity, and Mortality in US Adults With and Without Chronic Kidney Disease

IntroductionIn predialysis chronic kidney disease (CKD), the association of muscle mass with mortality is poorly defined, and no study has examined outcomes related to the co-occurrence of low muscle mass and excess adiposity (sarcopenic obesity).MethodsWe examined abnormalities of muscle and fat mass in adult participants of the National Health and Nutrition Examination Survey 1999–2004. We determined whether associations of body composition with all-cause mortality differed between participants with CKD compared to those without.ResultsCKD modified the association of body composition with mortality (P = 0.01 for interaction). In participants without CKD, both sarcopenia and sarcopenic obesity were independently associated with increased mortality compared with normal body composition (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.07–1.93, and HR = 1.64, 95% CI = 1.26–2.13, respectively). These associations were not present among participants with CKD. Conversely, obese persons had the lowest adjusted risk of death, with an increased risk among those with sarcopenia (HR = 1.43, 95% CI = 1.05–1.95) but not sarcopenic-obesity (P = 0.003 for interaction by CKD status; HR = 1.21, 95% CI = 0.89–1.65), compared with obesity.DiscussionSarcopenia associates with increased mortality regardless of estimated glomerular filtration rate, but excess adiposity modifies this association among persons with CKD. Future studies of prognosis and weight loss and exercise interventions in CKD patients should consider muscle mass and adiposity together rather than in isolation.

Secretory activity of subcutaneous abdominal adipose tissue in male patients with rheumatoid arthritis and osteoarthritis - association with clinical and laboratory data.

IntroductionAdipose tissue exerts widespread effects on the metabolism and immune system, but its activity differs between the genders. In the general population low-grade adipose tissue inflammation contributes to development of diseases of affluence. Little is known about the systemic impact of peripheral fat tissue in osteoarthritis (OA) and rheumatoid arthritis (RA), characterized by chronic, low- and high-grade systemic inflammation, respectively. To clarify this we evaluated the secretory activity of subcutaneous abdominal adipose tissue (SAAT) obtained from male patients affected with RA (n = 21) and OA (n = 13), and assessed its association with body mass and composition, demographic, clinical and laboratory data.Material and methodsBasal and interleukin (IL)-1β-triggered secretion of selected adipocytokines from SAAT explants was measured by specific enzyme-linked immunosorbent assays (ELISA). Patients’ body composition was evaluated by bioelectric impendence technique.ResultsRheumatoid SAAT secreted more adiponectin and macrophage migration inhibitory factor (MIF) than respective osteoarthritis tissue. In both RA and OA patient groups, stimulation of SAAT explants with IL-1β (1 ng/ml/100 mg tissue) significantly up-regulated release of pro-(IL-6, IL-8, tumor necrosis factor – TNF) and anti-inflammatory (IL-10) cytokines but had no effect on the secretion of adiponectin, leptin, MIF and hepatocyte growth factor (HGF). Compared with RA, patients with OA were more obese. In RA patients SAAT-released adiponectin and TNF inversely correlated with body mass index (BMI) and visceral fat rating (FVSC). In addition, SAAT-secreted adiponectin and leptin positively correlated with DAS28 and disease duration, respectively. In the OA group tissue-released TNF positively correlated with patients’ age.ConclusionsWe conclude that in RA male patients adipocytokines originating from SAAT are of clinical importance because: (i) adiponectin and TNF may contribute to maintenance of normal body composition and mass, (ii) in addition adiponectin may play a pathogenic role. Moreover, in both RA and OA male patients secretory activity of SAAT may vary with time.

Influence of body weight on bone mass, architecture and turnover.

Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating the development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. Although the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size.

Sarcopenic Obesity, Functional Outcomes, and Systemic Inflammation in Patients With Chronic Obstructive Pulmonary Disease

BackgroundBoth loss of muscle mass (ie, sarcopenia) and obesity adversely impact clinically important outcomes in patients with chronic obstructive pulmonary disease (COPD). Currently, there are only a few studies in patients with COPD with sarcopenia and concurrent obesity, termed sarcopenic obesity (SO). ObjectiveTo explore the effects of SO on exercise capacity, health status, and systemic inflammation in COPD. Design/Settings/ParticipantsBaseline data collected from a total of 2548 participants (2000 patients with COPD, mean age (SD), 63.5 (7.1) years; and 548 controls, 54.8 (9.0) years) from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study, a multicenter longitudinal observational study, were used. MeasurementsAll participants were divided into 4 body composition phenotypes using bioelectrical impedance analysis: (1) normal body composition, (2) obesity, (3) sarcopenia, and (4) SO. In patients with COPD, the 6-minute walking distance, disease-specific health status, and plasma inflammatory markers were compared among the respective body composition groups. ResultsPatients with COPD were 3 times more likely to present with SO compared with controls without COPD (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.0–5.4, P < .001). In patients with COPD, SO was related to reduced 6-minute walking distance (−28.0 m, 95% CI −45.6 to −10.4), P < .01) and to higher systemic inflammatory burden (an elevation of at least 2 inflammatory markers, OR 1.6, 95% CI 1.1–2.5, P = .028) compared with the normal body composition group after adjustments for age, sex, smoking, body mass index, and airflow limitation. ConclusionsOur findings suggest that SO is associated with worse physical performance and higher systemic inflammatory burden compared with other body composition phenotypes in patients with COPD. Trial registryClinicalTrials.gov no. NCT00292552.

Sarcopenia and Sarcopenic Obesity Are Prognostic Factors for Overall Survival in Patients with Cirrhosis.

Although the prognosis is known to be poor in cirrhosis patients associated with sarcopenia, the relationships among skeletal muscle, visceral fat, and the liver have not yet been thoroughly investigated. Therefore, the prognosis and its associations with body composition and the severity of liver disease were examined in patients with cirrhosis. The skeletal muscle mass and visceral fat area were measured in 161 patients with cirrhosis, the effects of body composition on the prognosis were analyzed, and any factors that contribute to changes in body composition were assessed. During the mean observation period of 1,005 days, 73 patients died. Patients with sarcopenia or sarcopenic obesity had a poor prognosis, and this difference was pronounced in the subset of patients classified as Child-Pugh class A. A decreased skeletal muscle mass was strongly correlated with decreased serum albumin levels. Sarcopenia is a common feature of advanced cirrhosis, and transitions were observed from normal body composition to sarcopenia and from obese to sarcopenic obesity. The body composition is a prognostic factor for cirrhosis, and a better body composition may be advantageous for obtaining a long-term survival in patients with cirrhosis.

Abstract 1153: Effective treatment of cancer associated cachexia by AV-380, a GDF15 inhibitory antibody

Abstract Background: One of the most lethal and debilitating effects of cancer is the development of cancer-related anorexia-cachexia syndrome (CACS). It affects the majority of advanced cancer patients and is thought to be responsible for up to ∼30% of all cancer deaths. CACS is a complex metabolic syndrome associated with malnutrition and severe involuntary weight loss due to the loss of muscle and fat tissue, as well as the clinical manifestation of anemia, inflammation and suppression of immune functions. The precise molecular mechanisms responsible for cancer cachexia are poorly understood, thus limiting the development of effective therapeutics. Current evidence suggests that a pro-inflammatory state may be responsible for many of the symptoms associated with CACS. Growth Differentiation Factor 15 (GDF15) is a pro-inflammatory cytokine whose circulating levels are significantly increased in cachectic cancer patients and several animal models of cancer cachexia. Here we demonstrate that the inhibition of GDF15 function results in the compete reversion of the phenotypic and metabolic changes associated with CASC. Methods: Mice bearing HT-1080 human fibrosarcoma xenografts have increased plasma GDF15 levels and develop cachexia were used in this study. Tumor bearing animals were treated either with AV-380, a GDF15 neutralizing antibody or IgG1 control. The effect on body weight, muscle/fat mass and organ sizes were assessed. Metabolic changes induced by the treatment were measured by a comprehensive laboratory animal monitoring system (CLAMS). Results: Treatment with AV-380 restored body weight, muscle and fat mass as well as normal organ sizes. Analyses of the CLAMS data demonstrated that mice receiving AV-380 reversed the phenotypic and metabolic changes associated with the cachexia induced by this tumor model. Moreover, AV-380 treated mice showed an increase in locomotor activity and energy expenditure, achieving levels similar to non tumor bearing control animals. Conclusions: Inhibition of GDF15 function completely reverted body weight loss, restored normal body composition and triggered a catabolic to anabolic metabolic switch in this cancer cachexia model. The data highlights the therapeutic potential of the GDF15 inhibitory antibody AV-380 for the treatment for CACS. Citation Format: Lorena Lerner, Nianjun Tao, Brian Krieger, Richard Nicoletti, Bin Feng, Nesreen Ismail, William Winston, Yanyu Zhang, Jinwei Jiang, Solly Weiler, Jeno Gyuris. Effective treatment of cancer associated cachexia by AV-380, a GDF15 inhibitory antibody. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1153. doi:10.1158/1538-7445.AM2015-1153

Effects of sitting time associated with media consumption on physical activity patterns and daily energy expenditure of Saudi school students.

[Purpose] This study was performed to assess the effect of daily sitting time during media consumption on physical fitness, total energy expenditure (TEE), and body composition indices of Saudi school children. [Subjects and Methods] A total of 180 healthy Saudi school students (8–18 years) were included in this study. Sitting time, total energy expenditure, and levels of physical activity were evaluated with pre-validated internet based questionnaires. Body composition indices were evaluated using anthropometric analysis. [Results] Out of the studied participants, only 22.2% of students were physically inactive. Children with moderate and active physical scores demonstrated less sedentary behavior (TV viewing and computer usage), lower body composition values (BMI, WC, WHtR), and higher TEE than sedentary or mild activity level participants. Boys showed higher fitness scores and less sedentary behavior than girls. Media sitting time among the studied subjects correlated negatively with physical scores and positively with body composition. [Conclusion] The data presented here suggests that poor physical fitness, lower TEE, and longer sitting times differentially influence normal body composition indices among school children which may lead to overweight or obese individuals. Thus, decreasing sitting time during media consumption and enhancing physical activity may play a pivotal role in preventing obesity in young children.