Diet quality and social support play essential roles in maintaining the health of older adults. However, the relationship between these factors remains uncertain. This study aimed to investigate the association between social support and dietary quality among community-dwelling older adults in China. This study analyzed 515 community-dwelling older adults from three districts in Shanghai that were selected based on their geographic location and level of economic development between March and November 2022. Dietary quality was assessed using the China Elderly Dietary Guideline Index (CDGI), China Healthy Eating Index (CHEI), and Dietary Inflammatory Index (DII). Social support was measured using the Social Support Rating Scale (SSRS). Associations between dietary quality and social support were examined using linear regression models. Participants had a mean age of 71.3 ± 4.7 years, and 39.4% were male. The mean CDGI, CHEI, and DII scores were 76.35 ± 11.38, 63.87 ± 9.75, and 0.57 ± 1.65, respectively. The mean SSRS score was 35.05 ± 7.54, ranging from 30.86 to 105.61. Correlation analysis showed that CDGI positively correlated with SSRS and CHEI but negatively correlated with DII. Participants in the highest CDGI tertile reported lower total fat intake and higher consumption of anti-inflammatory foods and nutrients compared to those in the lowest tertile. After adjusting for confounding factors, a higher CDGI score was significantly associated with higher SSRS scores (β = 0.094, 95% CI: 0.056-1.679, p = 0.036). Conversely, a lower DII score was significantly associated with higher SSRS scores (β = -0.088, 95% CI: -1.587 to -0.030, p = 0.042). These results showed that dietary quality and social support are positively correlated among older Chinese adults, highlighting the importance of strengthening social networks to promote healthier diets. These findings underscore the potential for community-based interventions targeting social and nutritional factors to be correlated with improved health outcomes in aging populations.

Sarcopenia is an age-related condition characterized by a decline in skeletal muscle mass and function, leading to impaired mobility and an increased risk of adverse health outcomes. However, the neuromuscular mechanisms underlying gait dysfunction in sarcopenia remain incompletely understood. In this study, individuals with sarcopenia and age-matched healthy controls were recruited. Gait parameters were assessed using a motion capture system and quantified through spatiotemporal analysis, muscle activity was evaluated using surface electromyography (sEMG) with phase-specific activation metrics, and cortical activity was measured using electroencephalography (EEG) and further analyzed using spectral analysis and partial directed coherence (PDC)-based graph-theoretical measures to assess frequency-specific functional connectivity. Individuals with sarcopenia exhibited significantly reduced gait speed and shorter step length, along with prolonged loading response and pre-swing phases. Among the recorded muscles, the tibialis anterior (TA) showed significant alterations, characterized by an increased and earlier first activation peak and a reduced and delayed second peak during the gait cycle. Phase-specific analysis revealed increased TA activity during the loading response phase and decreased activity during the pre-swing phase. EEG analysis revealed beta-band-specific alterations, with increased node strength and node degree in the frontal and central regions and elevated node strength in the parietal region, while no significant differences were observed in the delta, theta, alpha, or gamma bands. These findings suggest that sarcopenia is associated with neuromuscular alterations. The coexistence of increased beta-band functional connectivity strength and persistent gait impairment may reflect inefficient compensation, in which increased neural recruitment does not fully restore gait function. These results highlight the importance of targeting neuromuscular coordination in rehabilitation.

ABSTRACT Purpose To develop a chain mediation model to elucidate the relationship among physical performance, instrumental activities of daily living (IADL), regular exercise, and cognitive function among older adults who are comorbid with diabetes mellitus and hypertension (OA‐DM&HTN). Methods A total of 656 participants were investigated with the Mini‐Mental State Examination, the Short Physical Performance Battery, the Instrumental Activities of Daily Living, and a questionnaire on regular exercise frequency between January and September 2022. Sequential multiple mediation models were conducted to analyze the data. Results The average age of the participants was 73.47 ± 7.40 years, and 49.24% (n = 323) of participants were female. The average cognitive function score was 22.36 ± 6.14, and 32.62% (n = 214) of participants exhibited cognitive impairment. Cognitive performance exhibited significant associations with demographic factors, including gender, age, marriage status, educational background, and income level (p < 0.05). Chain mediation analysis indicated that physical performance directly predicted cognitive function (β = 0.525, 95% CI: 0.000–1.050); physical performance had indirect effects mediated by IADL (β = 0.917, 95% CI: 0.635–1.230) and regular exercise (β = 0.076, 95% CI: 0.003–0.180). A significant chain‐mediating effect involving both IADL and regular exercise was also observed on the relationship between physical performance and cognitive function (β = 0.034, 95% CI: 0.002–0.071). Conclusion Physical performance is a significant predictor of cognitive function, and it can also affect cognitive function through the independent or chain‐mediating effects of IADL and regular exercise among OA‐DM&HTN. Therefore, to delay cognitive decline among OA‐DM&HTN, it is essential to provide tailored functional training, encourage improvement in IADL, and promote regular exercise among OA‐DM&HTN.

Background & Aims The purpose of this study was to assess the association between N-terminal prohormone of type B natriuretic peptide (NT-proBNP) and long-term mortality in hospitalized oldest-old adults and to explore the mediating role of malnutrition and muscle loss. Methods This prospective cohort study was conducted among 360 hospitalized patients ≥ 80 years of age (median age 87 [IQR 84–90] years, 24.4% women) in the Department of Geriatrics. The Geriatric Nutritional Risk Index (GNRI) and Mini Nutritional Assessment Short Form (MNA-SF) were used for nutritional assessment, while calf circumference was used as a measure of muscle mass. A Cox proportional hazard model was used to assess the relationship between NT-proBNP levels and mortality. Mediation analysis was used to explore the mediating effects of malnutrition and muscle loss. Results The median follow-up was 4.1 years with 159 (44.1%) deaths. Mortality risk increased by 32% per 2-fold increase in NT-proBNP levels (full adjusted hazard ratio: 1.32 [95% CI, 1.20–1.46]). A mediation analysis showed that a lower GNRI score and decreased calf circumference mediated the effects of high NT-proBNP and mortality risk, with an estimated relative effect size of 28.9%, while MNA-SF and calf circumference mediated the effect, with an estimated relative effect size of 25.3%. Conclusions NT-proBNP levels were associated with long-term mortality in hospitalized older patients. Moreover, the detrimental effects of NT-proBNP on survival were partly mediated by malnutrition and muscle loss.

The aim of this study was to determine whether low calf circumference (CC) could predict nutritional risk and the cut-off value of CC in type 2 diabetes (T2D) older patients. We also aimed to evaluate the risk factors for predicting mortality in T2D. A total of 296 older patients with T2D were enrolled in this study and followed for 2.5 years at the longest. The CC level was significantly lower in the nutritional risk group than in the non-nutritional risk with T2D group (26.7 ± 4.1 cm vs. 30.2 ± 3.9 cm, P < 0.001). Decreased CC (OR, 6.79; 95

Background:The dietary index of gut microbiota (DI-GM) was developed to assess dietary quality by reflecting the diversity of the gut microbiota composition. This study examined the relationship between DI-GM and sarcopenia risk and evaluated the potential moderating effects of diet-related factors on sarcopenia risk in adult individuals. Methods:This cross-sectional study included 8,872 adults from the National Health and Nutrition Examination Survey (NHANES) database between 2011 and 2018. Weighted multivariable logistic regression, restricted cubic splines (RCS), and subgroup analyses were used to investigate the association between DI-GM and sarcopenia. Mediation analysis was employed to examine the impact of the dietary inflammatory index (DII), systemic immune-inflammatory index (SII), and body mass index (BMI) on the relationship between DI-GM and sarcopenia. Results:Among the eligible participants, 773 (8.71%) had sarcopenia. The mean DI-GM value was significantly lower in the sarcopenia group than in the non-sarcopenia group (4.76 vs. 4.99, p < 0.001). Multivariable logistic regression analysis revealed a negative association between DI-GM and the risk of sarcopenia, irrespective of whether the independent variable was analyzed as a continuous variable or in quartiles in the fully adjusted model (Model 3, continuous variable: OR = 0.91, 95% confidence interval (CI): 0.88-0.95, p < 0.001; Q4 vs. Q1: OR = 0.67, 95% CI = 0.56-0.80, p < 0.001, p for trend<0.001). The RCS curves illustrated a non-linear relationship between DI-GM and sarcopenia risk. Subgroup analyses indicated an inverse relationship between DI-GM and sarcopenia risk across various covariates in the study. Mediation analysis demonstrated that 46.32, 2.29, and 29.63% of the association between DI-GM and sarcopenia was mediated by the DII, SII, and BMI, respectively. Conclusion:A lower DI-GM score was strongly associated with an increased risk of sarcopenia, particularly among older adults, women, individuals with hypertension, and individuals with reduced physical activity. The DII and BMI may mediate the relationship between DI-GM and sarcopenia risk, suggesting that a diet promoting gut health could be an effective strategy for preventing sarcopenia. Additional longitudinal or interventional studies are required to substantiate the findings of this study.

OBJECTIVE:The study assessed the association between diabetes and both the quantity and quality of skeletal muscle among older adults, based on an analysis of chest computed tomography (CT) scans. METHODS:In this cross-sectional study of 1225 adults aged 65 years or more, 255 had type 2 diabetes mellitus. All participants had chest CT scans. Skeletal muscle index and skeletal muscle density at the level of the fourth thoracic vertebra were assessed using SliceOmatic software. RESULTS:Skeletal muscle density at the fourth thoracic level was significantly lower in the diabetes group, while no significant difference between groups was observed in the muscle index. Spearman correlation analysis showed no significant correlation between fasting plasma glucose or glycated hemoglobin and the muscle index. However, both fasting plasma glucose and glycated hemoglobin were negatively correlated with skeletal muscle density (rho = -0.100 and -0.194, respectively; both P < 0.05). After adjusting for potential confounders, linear regression analysis indicated that diabetes was negatively associated with skeletal muscle density (β = -0.069, P = 0.002). Logistic regression analysis identified skeletal muscle density as a significant independent factor associated with diabetes (OR = 0.943, 95 % confidence interval 0.908-0.979, P = 0.002). CONCLUSION:Based on chest CT scan, diabetes exerts a discernible impact on the quality of skeletal muscle (skeletal muscle density) at the fourth thoracic level among older adults, rather than its quantity (skeletal muscle index). These insights can inform clinical interventions and disease management strategies.

Sarcopenia is an age-related disorder that influences the daily living ability of older adults and interacts with various chronic diseases. Older adults with sarcopenia typically experience a deterioration in their quality of life and healthy lifespan. The number of Chinese persons with sarcopenia is considerable, and the burden of sarcopenia is substantial; however, the specific sarcopenia clinics available for outpatients are insufficient. The promotion of sarcopenia clinics is beneficial for the early identification, standardized diagnosis, and treatment of older adults with sarcopenia, thereby helping to enhance their physical function and quality of life. This consensus incorporates the professional recommendations of Chinese geriatrics experts, synthesizes existing Chinese experiences in establishing sarcopenia clinics, offers guidance for managing sarcopenia clinics, and advocates for early identification, diagnosis, and intervention of sarcopenia in older adults.

Abstract Background Diabetic peripheral neuropathy(DPN) is one of the most common complications of diabetes. In this study, we investigated the potential role of H2S as a novel therapy for DPN in diabetic rats. Method All the rats were divided into non-diabetic control group(n = 10), diabetic control group (n = 10) and H2S treated diabetic group (n = 10). A single dose of streptozotocin (60mg/kg) was applied to the rats for the diabetic models. Sodium bisulfide (50µmol/kg/d) was intraperitoneally injected daily for 2 weeks as H2S treatment. Biochemical assay, electromyogram, hematoxylin eosin (HE) staining, transmission electron microscopy, western blot and enzyme linked immunosorbent assay (ELISA) were then performed. Results H2S treatment did not affect the body weight, blood glucose levels or liver and kidney function in diabetic rats. Cell atrophy and axon degeneration of sciatic nerve and dorsal root ganglion (DRG) in diabetic rats were relieved after H2S treatment through observation of light microscopy and transmission electron microscopy. Furthermore, superoxide dismutase levels in serum and superoxide dismutase2 in sciatic nerve of diabetic rats were lower than non-diabetic rats, but restored obviously after H2S treatment. Serum and sciatic nerve homogenate malondialdehyde and aldose reductase expression were obviously higher in diabetic rats, but decreased significantly after H2S treatment. Finally, the sciatic nerve conduction velocity of diabetic rats improved after H2S treatment compared with diabetic control group, however without statistical significance. Conclusions Our study revealed that H2S alleviates neural degeneration in diabetic rats probably through reducing oxidative stress and downregulating aldose reductase expression.

BACKGROUND:The physical function of elderly individuals reflects whether they have had a history of regular physical activity over the long term. Such indicators have been found to have a certain connection with cognitive function these years. However, there is limited research that associates it with mechanisms such as cerebral Aβ deposition. We aim to investigate this relationship and unveil the underlying mechanisms. METHOD:Physical function and cognition data of 4189 participants were obtained from the Chinese preclinical Alzheimer's disease study. Participants were divided into six groups according to disease severity. Among them, 1048 participants underwent the positron emission tomography-computed tomography (PET-CT) and plasma biomarker test. Grip strength and gait were combined into a score indicating physical function. Multiple linear regression models and logistic regression models were mainly used to conduct the analysis. RESULTS:There was a significant positive correlation between physical function and cognitive function (R = 0.48, p < 0.001), independent of sex, age, apolipoprotein E-ε4 genotype, and disease stages (p < 0.001). Physical function was effective in distinguishing individuals with cognitive impairment from those without (AUC = 0.835). Physical function was negatively associated with brain Aβ deposition (p = 0.008) and brain Aβ had an intermediary effect (p < 0.01) on the association between physical function and cognition in women. This association was mainly evident in the lateral parietal, lateral temporal, posterior cingulate, frontal, occipital, and precuneus regions. Physical function was negatively associated with plasma neurofilament light-chain (Nfl) level (p < 0.001). CONCLUSIONS:Physical function is strongly associated with cognitive function in the Chinese elderly, and brain Aβ deposition partly mediates the linkage in women. Plasma Nfl can be used as a potential target for exercise intervention in cognitive function. Improving physical function will contribute to the alleviation of cognition decline.

Objective: To determine reference values for diagnosing sarcopenia through chest CT scans and evaluate their suitability for use among the Chinese old population. Methods: Chest CT scans were obtained from 500 healthy individuals aged 19-39. Skeletal muscle mass was assessed on chest CT at the level of T4 by the skeletal muscle area (T4SMA), skeletal muscle index (T4SMI), T12 erector spinae muscle area (T12ESMA), and T12 skeletal muscle index (T12SMI), as well as skeletal muscle density (SMD) at T4 and T12 levels. The diagnostic threshold for sarcopenia was defined as a gender-specific value below 2 SD of the mean value in the young group. These cutoff values were then applied to a group of older adults aged 65 and over. Results: Diagnostic thresholds for low skeletal muscle in men were 110.05 cm(2), 36.01 cm(2)/m(2), 29.56 cm(2), and 9.65 cm(2)/m(2) for T4SMA, T4SMI, T12ESMA, and T12SMI, respectively. For women, the thresholds were: 69.93 cm(2), 26.51 cm(2)/m(2), 17.84 cm(2)/m(2), and 6.87 cm(2)/m(2), respectively. Diagnostic thresholds for low SMD were 38.63HU in men, 34.74 HU for women at T4 level. At T12 level, the cutoff values were 40.94 HU for men and 36.63 HU for women. Sarcopenia prevalence in men, defined by T4SMA, T4SMI, T12ESMA, and T12SMI cutoffs, was 35.6%, 18.9%, 36.7%, and 23.7%, respectively. In women, sarcopenia prevalence was 5.1%, 3.2%, 3.2%, and 1.9%, respectively. Conclusion: This study established reference values for sarcopenia diagnosis through chest CT scans among the Chinese population, highlighting the importance of utilizing chest CT scans for sarcopenia detection and muscle health monitoring in older adults. (c) 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Sarcopenia is a muscle disease that can lead to a decrease in muscle mass and strength. Patients with sarcopenia usually have gait disorders and a higher risk of falls. At present, muscle activation of lower limb during walking in patients with sarcopenia is not clear, making it difficult to find effective rehabilitation training. In this study, we aim to investigate muscle activation of lower limb during walking in elderly individuals with sarcopenia. We collected surface EMG signals from the tibialis anterior (TA), lateral gastrocnemius (GL), rectus femoris (RF), and biceps femoris (BF) muscles during walking. Results showed that differences of muscle activation between sarcopenia patients and healthy elderly during walking are mainly reflected in the shank. Specially, RMS of TA was statistically significantly higher in sarcopenia patients during swing phase (p=0.005). Modulation index of GL was significantly higher in sarcopenia patients during pre-swing phase (p=0.01). Coactivation index of TA-GL was significantly lower in sarcopenia patients during single stance phase. A significant strong correlation was also observed between RMS of GL and step length (r=0.863, p=0.012) in sarcopenia patients. These results indicated that differences of muscle activation in shank may contribute to gait disorders in sarcopenia patients. It is recommended that exercise intervention strategies for sarcopenia patients should focus on shank muscles.

Abstract Objective Thyroid hormones stimulate myogenesis and muscle contraction and regulate skeletal muscle cell metabolism. However, the association between thyroid hormone levels and mortality in sarcopenic older adults remains elusive. The aim of this study was to investigate the relationship between thyroid hormones and all-cause mortality in people over 80 years of age with sarcopenia. Methods This study was performed on 264 sarcopenic patients aged 80 years and older. Serum levels of thyroid hormone, including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) were tested to evaluate thyroid status. Sarcopenia was defined using the criteria of the European Working Group on Sarcopenia in Older People. Mortality data were available for up to 38 months of follow-up. The correlation between FT3 and calf circumference (CC) or handgrip strength (HGS) was determined by Pearson correlation analysis. Kaplan-Meier analysis was used to compare the differences between FT3 tertile groups. Cox regression was used to analyze the mortality risk ratio of patients with different FT3 tertiles. Results During the follow-up period, 88 older adults died. Non-Survivors had lower serum FT3 levels (3.7 ± 0.5 vs. 3.9 ± 0.7, P = 0.001) than the Survivor. Serum FT3 was positively associated with CC and HGS (r = 0.29, P < 0.001, r = 0.21, P = 0.002, respectively). The Kaplan-Meier curve analysis demonstrated a difference in mortality among the FT3 tertile groups (log-rank test, χ2 = 11.83, P = 0.003). The high FT3 group had lower mortality compared with the low FT3 group (the adjusted HRs were 0.63 (95%CI: 0.41–0.96 P = 0.031). Conclusion Lower FT3 within the reference range is associated with higher mortality in adults over 80 years with sarcopenia and euthyroid. Routine assessment of FT3 may be an easy way to identify high-risk older adults with sarcopenia.

Objective: Sarcopenia is a prevalent condition in the senior population and has been related to adverse outcomes. This study aimed to investigate the performance of the serum creatinine/ cystatin C ratio (Cr/CysC) in predicting all-cause mortality in elders over 80 years.Methods: A total of 486 older patients over 80 were enrolled in this study. Calf circumference (CC) and handgrip strength (HGS) were carried out for each patient. All the participants accepted serum creatinine and cystatin C test. The primary clinical outcome was all-cause mortality during an over-4-year follow-up.Results: During an over 4-year follow-up, 200 participants died. The non-survivors had a signif-icantly lower baseline Cr/CysC level than the survivors (62.6 +/- 13.1 vs. 71.4 +/- 14.5 P < 0.001). The lowest Cr/CysC quartile group (Q1) had a significantly higher mortality rate than their counterparts (Q1 vs. Q2-4, 62.8% vs. 33.2%, P < 0.001). The Cr/CysC level was positively correlated with CC (R2 = 0.17, P < 0.001) and HGS (R2 = 0.19, P < 0.001). Moreover, survival curve was significantly worse in the lowest Cr/CysC quartile (Log-rank test chi 2 = 21.09, P < 0.001). After adjustment for potential confounders, age (HR, 1.10; 95% CI, 1.06-1.14, P < 0.001), coronary heart disease (HR, 1.49; 95% CI, 1.01-2.21, P = 0.045), and lowest Cr/CysC (HR, 1.59; 95% CI, 1.12-2.24, P = 0.009) were independent factors of all-cause mortality during the over-4 -year follow-up.Conclusion: Cr/CysC, also known as Sarcopenia Index, could be used as a predictor of all-cause mortality in older adults over 80 years.

Background: Sarcopenia is a geriatric syndrome characterized by progressive loss of muscle mass, function and quality and associated with a range of adverse health outcomes including disability. Despite a negative correlation between muscle mass and follicle-stimulating hormone (FSH) levels in postmenopausal women, it is unclear if FSH is associated with sarcopenia and its poor outcomes, especially in older men. Methods: We used cross-sectional data from 360 men aged over 80 who participated in health check-ups to investigate correlations between serum FSH and sarcopenia, individual sarcopenia components, low physical performance (gait speed ≤ 0.8 m/s) and instrumental activities of daily living (IADL) disability. Sarcopenia and severe sarcopenia were diagnosed according to the revised definition of the European Working Group on Sarcopenia in Old People (EWGSOP2). Results: The prevalence of sarcopenia was 17.8% in this population. In binary logistic regression analysis, compared with higher FSH group, lower FSH group showed a significant reduction in the risk of low calf circumference (a surrogate for muscle mass; OR 0.308, 95% CI 0.109–0.868, P = 0.026) after adjusting potential confounders including age, waist circumference, education, exercise, associated biochemical parameters, other sex hormones and high-sensitivity C-reactive protein. The correlation between FSH and low handgrip strength was marginally significant (OR 0.390, 95% CI 0.151–1.005, P = 0.051). No associations were observed between FSH and sarcopenia, severe sarcopenia, and disability in adjusted models. Conclusion: In older men, circulating FSH was not associated with sarcopenia, sarcopenia severity, the majority of its components and adverse health outcome (IADL disability), with the exception of low calf circumference. Further work is needed to better elucidate the association of FSH and low muscle quantity by adopting more accurate measurement method of appendicular skeletal muscle mass such as DXA, CT or MRI.

Obesity is associated with several skeletal muscle impairments which can be improved through an aerobic exercise prescription. The possibility that exercise responsiveness is diminished in people with obesity has been suggested but not well‐studied. The purpose of this study was to investigate how obesity influences acute exercise responsiveness in skeletal muscle and circulating amino metabolites. Non‐obese (NO; n = 19; 10F/9M; BMI = 25.1 ± 2.8 kg/m2) and Obese (O; n = 21; 14F/7M; BMI = 37.3 ± 4.6 kg/m2) adults performed 30 min of single‐leg cycling at 70% of VO2peak. 13C6‐Phenylalanine was administered intravenously for muscle protein synthesis measurements. Serial muscle biopsies (vastus lateralis) were collected before exercise and 3.5‐ and 6.5‐h post‐exercise to measure protein synthesis and gene expression. Targeted plasma metabolomics was used to quantitate amino metabolites before and 30 and 90 min after exercise. The exercise‐induced fold change in mixed muscle protein synthesis trended (p = 0.058) higher in NO (1.28 ± 0.54‐fold) compared to O (0.95 ± 0.42‐fold) and was inversely related to BMI (R2 = 0.140, p = 0.027). RNA sequencing revealed 331 and 280 genes that were differentially expressed after exercise in NO and O, respectively. Gene set enrichment analysis showed O had six blunted pathways related to metabolism, cell to cell communication, and protein turnover after exercise. The circulating amine response further highlighted dysregulations related to protein synthesis and metabolism in adults with obesity at the basal state and in response to the exercise bout. Collectively, these data highlight several unique pathways in individuals with obesity that resulted in a modestly blunted exercise response.

Objective: The health benefits of exercise are well documented, but several exercise-response parameters are attenuated in individuals with obesity. The goal of this pilot study was to identify molecular mechanisms that may influence exercise response with obesity. Methods: A multi-omics comparison of the transcriptome, proteome, and phosphoproteome in muscle from a preliminary cohort of lean individuals (n = 4) and individuals with obesity (n = 4) was performed, before and after a single bout of 30 minutes of unilateral cycling at 70% maximal oxygen uptake (VO2 peak). Mass spectrometry and RNA sequencing were used to interrogate the proteome, phosphoproteome, and transcriptome from muscle biopsy tissue. Results: The main findings are that individuals with obesity exhibited transcriptional and proteomic signatures consistent with reduced mitochondria! function, protein synthesis, and glycogen synthesis. Furthermore, individuals with obesity demonstrated markedly different transcriptional, proteomic, and phosphoproteomic responses to exercise, particularly biosynthetic pathways of glycogen synthesis and protein synthesis. Casein kinase II subunit alpha and glycogen synthase kinase-3 beta signaling was identified as exercise-response pathways that were notably altered by obesity. Conclusions: Opportunities to enhance exercise responsiveness by targeting specific molecular pathways that are disrupted in skeletal muscle from individuals with obesity await a better understanding of the precise molecular mechanisms that may limit exercise-response pathways in obesity.

TNF-alpha is a potent pro-inflammatory cytokine. Previous studies have proved that biallelic polymorphisms in the TNF-alpha (-308, TNFA) and TNF-beta genes (intron 1, TNFB) influence TNF-alpha production. In sarcoidosis, a chronic granulomatous disease, as a result of an unknown in vivo activation bronchoalveolar lavage (BAL) cells release high amounts of TNF-alpha, spontaneously and after in vitro stimulation. Thus, sarcoidosis could serve as a model to test the in vivo effect of TNF gene polymorphisms. We determined the TNFA and TNFB polymorphisms of 44 patients with sarcoidosis and found the following allele frequencies: 0.80, 0.20, 0.38 and 0.62 for TNFA1, TNFA2, TNFB1 and TNFB2, respectively. To examine the in vivo effect of the named polymorphisms on the TNF-alpha production, the spontaneous and LPS-induced TNF-alpha release of BAL cells and peripheral blood mononuclear cells were also determined in patients with sarcoidosis. Statistical analysis did not reveal any significant difference between sarcoidosis patients with different genotypes. The results show that TNFA and TNFB polymorphisms do not determine the level of TNF-alpha release of mononuclear cells activated during the course of sarcoid inflammation.

These data highlight several unique pathways in individuals with obesity that result in a blunted exercise response.