Muscle Mass Research Articles

Lower creatinine-to-cystatin c ratio associated with increased risk of incident amyotrophic lateral sclerosis in the prospective UK biobank cohort.

Reduced muscle mass has been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, it remains unclear whether decreased muscle mass is a risk factor for ALS or a consequence of motor neuron degeneration. Recently, serum creatinine-to-cystatin C ratio (CCR) have emerged as promising biomarkers for assessing muscle mass. We aimed to explore the association between CCR and the incidence of ALS using data from the UK Biobank. Between 2006 and 2010, 446,945 participants were included in the baseline. CCR was calculated as the ratio of serum creatinine to cystatin C. Cox regression models were used to analyze the relationship between CCR and ALS incidence. Furthermore, subgroup analyses were conducted to investigate potential covariates in these relationships. After adjusting for all covariates, the multivariate Cox regression analysis revealed a significant association between decreased CCR and an increased risk of ALS (hazard ratio (HR) = 0.990, 95% confidence interval (CI): 0.982-0.999, P = 0.026). Participants were stratified into groups based on CCR tertiles. Compared with participants in the highest tertiles of CCR, those in the lowest (HR = 1.388, 95% CI: 1.032-1.866, P = 0.030) and medium tertiles (HR = 1.348, 95% CI: 1.045-1.739, P = 0.021) had an increased risk of ALS incidence. Subgroup analysis showed that the relationship between CCR and ALS incidence was particularly significant among participants aged < 65years (CCR tertile 1: HR = 1.916, 95% CI: 1.366-2.688, P < 0.001; CCR tertile 2: HR = 1.699, 95% CI: 1.267-2.278, P < 0.001). The present results demonstrate that lower CCR is significantly associated with a higher risk of ALS.

Enduring effects of acute prenatal ischemia in rat soleus muscle, and protective role of erythropoietin.

Motor disorders are considered to originate mainly from brain lesions. Placental dysfunction or maternal exposure to a persistently hypoxic environment is a major cause of further motor disorders such as cerebral palsy. Our main goal was to determine the long-term effects of mild intrauterine acute ischemic stress on rat soleus myofibres and whether erythropoietin treatment could prevent these changes. Rat embryos were subjected to ischemic stress at embryonic day E17. They then received an intraperitoneal erythropoietin injection at postnatal days 1-5. Soleus muscles were collected at postnatal day 28. Prenatal ischemic stress durably affected muscle structure, as indicated by the greater fiber cross-sectional area (+ 18%) and the greater number of mature vessels (i.e. vessels with mature endothelial cells) per myofibres (+ 43%), and muscle biochemistry, as shown by changes in signaling pathways involved in protein synthesis/degradation balance (-81% for 4EBP1; -58% for AKT) and Hif1α expression levels (+ 95%). Erythropoietin injection in ischemic pups had a weak protective effect: it increased muscle mass (+ 25% with respect to ischemic pups) and partially prevented the increase in muscle degradation pathways and mature vascularization, whereas it exacerbated the decrease in synthesis pathways. Hence, erythropoietin treatment after acute ischemic stress contributes to muscle adaptation to ischemic conditions.

Appendicular Skeletal Muscle Mass (ASMM) and Fat-Free Mass (FFM) DXA–BIA Estimations for the Early Identification of Sarcopenia/Low Muscle Mass in Middle-Aged Women

Background/Objectives: Sarcopenia involves the loss of muscle mass along with a decrease in muscle strength and physical performance. The aim of this paper was to compare the already published BIA equations for the estimation of Appendicular Skeletal Muscle Mass (ASMM) and Fat-Free Mass (FFM) with dual X-ray densitometer DXA estimations in order to determine whether Bioelectrical Impedance Analysis (BIA) could be a feasible application on a general population for the detection of low muscle mass and sarcopenia. Methods: Seventy-nine healthy women aged 40–70 years were included. Assessments involved BIA and DXA evaluations and anthropometric measurements. Results: DXA and BIA estimations showed great agreement, particularly the ones introduced by Scafoglieri et al. (2017) for ASMM (mean difference 1.81 kg) and Kanellakis et al. (2020) equation for FFM (mean difference 0.52 kg) resulted in the best fit for the cohort in analysis. BIA could intercept a low muscle mass condition which can be linked to sarcopenia. Conclusions: This study showed how the use of BIA represents an effective and reliable method in the evaluation of sarcopenia.

Role of myofiber-specific FoxP1 in pancreatic cancer-induced muscle wasting.

Cancer cachexia affects up to 80% of cancer patients and results in reduced quality of life and survival. We previously demonstrated that the transcriptional repressor Forkhead box P1 (FoxP1) is upregulated in skeletal muscle of cachectic mice and people with cancer, and when overexpressed in skeletal muscle is sufficient to induce pathological features characteristic of cachexia. However, the role of myofiber-derived FoxP1 in both normal muscle physiology and cancer-induced muscle wasting remains largely unexplored. To address this gap, we generated a conditional mouse line with myofiber-specific ablation of FoxP1 (FoxP1SkmKO) and found that in cancer-free mice, deletion of FoxP1 in skeletal myofibers resulted in increased myofiber size in both males and females, with a significant increase in muscle mass in males. In response to murine KPC pancreatic tumor burden, we found that myofiber-derived FoxP1 is required for cancer-induced muscle wasting and diaphragm muscle weakness in male mice. In summary, our findings identify myofiber-specific FoxP1 as a negative regulator of skeletal muscle with sex-specific differences in the context of cancer.

Metabolomic characterization of unintentional weight loss among community-dwelling older Black and White men and women.

This study aims to understand the metabolic mechanisms of unintentional weight loss in older adults. We investigated plasma metabolite associations of subsequent weight change over 2 years in 1536 previously weight stable participants (mean age 74.6 years, 50% women, 35% Black) from the Health, Aging and Body Composition (Health ABC) Study. Multinomial logistic regressions were used to examine associations of the 442 metabolites with weight loss with/without an intention and weight gain >3% annually relative to weight stability. The metabolite associations of unintentional weight loss differed from those of intentional weight loss and weight gain. Lower levels of aromatic amino acids, phospholipids, long-chain poly-unsaturated triglycerides, and higher levels of amino acid derivatives, poly-unsaturated fatty acids, and carbohydrates were associated with higher odds of unintentional weight loss after adjusting for age, sex, race, and BMI categories. Prevalent diseases attenuated four and lower mid-thigh muscle mass and poorer appetite each attenuated 2 of 77 identified metabolite associations by >20%, respectively. Other factors (e.g., energy expenditure, diet, and medication) attenuated all associations by <20%. While 16 metabolite associations were attenuated by 20%-48% when adjusting for all these risk factors, 47 metabolite associations remained significant. Altered amino acid metabolism, impaired mitochondrial fatty acid oxidation, and inflammaging implicated by identified metabolites appear to precede unintentional weight loss in Health ABC older adults. Furthermore, these pathways seem to be associated with prevalent diseases especially diabetes, lower muscle mass, and poorer appetite.

No detectable loss of myonuclei from human muscle fibers after six weeks of immobilization following an Achilles tendon rupture.

Muscle disuse has rapid and debilitating effects on muscle mass and overall health, making it an important issue from both scientific and clinical perspectives. However, the myocellular adaptations to muscle disuse are not yet fully understood, particularly those related to the myonuclear permanence hypothesis. Therefore, in this study, we assessed fiber size, number of myonuclei, satellite cells, and capillaries in human gastrocnemius muscle after a period of immobilization following an Achilles tendon rupture. Six physically active patients (5M/1F, 43 {plus minus} 15 years) were recruited to participate after sustaining an acute unilateral Achilles tendon rupture. Muscle biopsies were obtained from the lateral part of the gastrocnemius before and after six weeks of immobilization using a plaster cast and orthosis. Muscle fiber characteristics were analyzed in tissue cross-sections and isolated single fibers using immunofluorescence and high-resolution microscopy. Immobilization did not change muscle fiber type composition nor cross-sectional area of type I or type II fibers, but muscle fiber volume tended to decline by 13% (p=0.077). After immobilization, the volume per myonucleus was significantly reduced by 20% (p=0.008). Myonuclei were not lost in response to immobilization but tended to increase in single fibers and type II fibers. No significant changes were observed for satellite cells or capillaries. Myonuclei were not lost in the gastrocnemius muscle after a prolonged period of immobilization, which may provide support to the myonuclear permanence hypothesis in human muscle. Capillaries remained stable throughout the immobilization period, whereas the response was variable for satellite cells, particularly in type II fibers.

Phase angle is a useful predicting indicator for protein-energy wasting and cardiovascular risk among maintenance hemodialysis patients.

Protein-energy wasting (PEW) is a major contributor to the high mortality among maintenance hemodialysis (MHD) patients. Cardiovascular disease (CVD) is the leading cause of death in dialysis patients, and PEW can significantly increase cardiovascular mortality in MHD patients. Previous studies have confirmed that PA may be a good objective indicator for determining the nutritional status and prognosis of MHD patients. Our study aimed to determine the predictive value of phase angle (PA) as detected by bioelectrical impedance analysis (BIA) on PEW and cardiovascular (CV) risk among MHD patients. Our retrospective observational study involved 161 adult patients with HD. The Cardiovascular risk score is a risk model based on the Japan Dialysis Outcome and Practice Patterns Study (J-DOPPS). We established LASSO logistic regression analysis model to identify key parameters related to body composition that can predict PEW in MHD patients. The area under the curve (AUC) values for PA, appendicular skeletal muscle mass index (ASMI), body cell mass (BCM), and mid-arm circumference (MAC) in predicting PEW in male MHD patients were relatively large, with 0.708, 0.674, 0.663, and 0.735, respectively. The predicted PEW values of these parameters were slightly lower in female patients than in men. We incorporated PA, ASMI, BCM, and MAC into a model that predicted the incidence of PEW in maintenance hemodialysis patients using LASSO technology. We discovered that the model predicted a greater AUC of PEW occurrence than any single factor, 0.877 for men and 0.76 for women. The results of the univariate logistic regression analysis showed that the low PA tertile array group had a greater incidence of PEW than the high PA group (P < 0.001). Additionally, we also found that lower PA was associated with higher CV risk scores. The PA detected by bioelectrical impedance analysis could predict the risk of PEW and cardiovascular events among patients with MHD. When used in conjunction, PA, ASMI, BCM, and MAC have a high diagnostic efficacy for PEW in patients on maintenance hemodialysis.

Tetrandrine induces muscle atrophy involving ROS-mediated inhibition of Akt and FoxO3.

Tetrandrine (Tet), a well-known drug of calcium channel blocker, has been broadly applied for anti-inflammatory and anti-fibrogenetic therapy. However, due to the functional diversity of ubiquitous calcium channels, potential side-effects may be expected. Our previous report revealed an inhibitory effect of Tet on myogenesis of skeletal muscle. Here, we found that Tet induced protein degradation resulting in the myofibril atrophy. Upon administration with a relative high dose (40mg/kg) of Tet for 28days, the mice displayed significantly reduced muscle mass, strength force, and myosin heavy chain (MyHC) protein levels. The MyHC reduction was further detected in C2C12 myotubes after treating with Tet. Interestingly, the expression of Atrogin-1 and Murf-1, the skeletal muscle specific E3 ligases of protein ubiquitin-proteasome system (UPS), was accordingly up-regulated, and the reduced MyHC was significantly mitigated by MG132, a 26S proteasome inhibitor, indicating a key role of UPS in the protein degradation of muscle cells. Further study showed that Tet induced autophagy also participated in the protein degradation. Mechanistically, Tet treatment caused ROS production in myotubes that in turn targeted on FoxO3/AKT signaling, resulting in the activation of UPS and autophagy processes that were involved in the protein degradation. Our study reveals a potential side-effect of Tet on skeletal muscle atrophy, particularly when the drug dose is relatively high.

ASO Author Reflections: Surgical Procedures for Early-Stage Lung Cancer Patients with Low Muscle Mass.

ASO Author Reflections: Surgical Procedures for Early-Stage Lung Cancer Patients with Low Muscle Mass.

Current approach to the diagnosis of sarcopenia in cardiovascular diseases

Muscle wasting syndrome, also known as sarcopenia, is an age-related geriatric condition characterized by a gradual loss of muscle mass, strength, and function. Sarcopenia can be classified into primary and secondary types. Primary sarcopenia is primarily associated with aging, while secondary sarcopenia is caused by systemic diseases such as cancer, diabetes, liver cirrhosis, musculoskeletal disorders, and disuse changes. In recent years, increasing evidence suggests that cardiovascular diseases can promote the occurrence of sarcopenia through various pathophysiological mechanisms. Additionally, sarcopenia increases the risk of adverse outcomes in patients with cardiovascular disease such as rehospitalization and mortality. Therefore, screening and diagnosing sarcopenia are particularly important for patients with cardiovascular diseases. This article provides a brief overview of the research progress on diagnostic methods for sarcopenia in patients with cardiovascular diseases.

Ultrasound assessment of muscle and fascia properties and the effects of spasticity and botulinum toxin injections on spastic muscles in chronic stroke survivors

Abstract Objective To objectively quantify changes in muscle properties in chronic stroke survivors and the effects of spasticity and botulinum toxin injections (BoNTi) on muscle properties using ultrasonography. Design In this cross-sectional observational study, 24 stroke subjects with history of BoNTi to biceps brachii muscles (BB) but without BoNTi to the triceps (TRI) were included. Results 12 subjects had spastic TRI, the other half did not. 20 subjects had spasticity in wrist flexors, and 11 subjects received BoNTi to the flexor carpii ulnaris (FCU). On average, a significant decrease in muscle thickness (16.5% loss in TRI), a thicker fascia with higher echo intensity were noted on muscles in the paretic limb. Percent muscle loss (PML) was significantly less (11.0%) in spastic TRI than in non-spastic TRI (22.1%). There was no statistically significant difference in muscle and fascia properties in spastic FCU with and without BoNTi. Spasticity did not correlate significantly with muscle loss, fascia thickness or echo intensity. Conclusion Our results provided evidence that muscles on the spastic-paretic side had less muscle mass, thicker fascia and greater echo intensity. Our results showed that spasticity helped maintain muscle mass, but failed to reveal additional muscle loss after botulinum toxin injection.

Different contributions of fat and lean indices to bone strength by sex.

Bone strength depends on both bone density and quality. However, the differences in how body composition indices affect bone strength between men and women remains unclear. This study investigated the associations of various fat and lean indices with bone strength by sex. In this cross-sectional study involving 1,419 participants, bone mineral density (BMD) and body composition were measured using dual-energy X-ray absorptiometry. Bone quality was assessed using the trabecular bone score (TBS). Fat indices included total fat mass, body fat percentage, and waist circumference, while lean indices included appendicular lean mass (ALM) and hand grip strength. All fat indices demonstrated a positive association with BMD and a negative association with the TBS in both men and women. Fat indices were more strongly associated with BMD in women than in men. Furthermore, lean indices contributed more to BMD in men than in women. In women, ALM contributed more to BMD than hand grip strength, whereas in men, hand grip strength had a greater impact on BMD than ALM. Hand grip strength was also positively associated with the TBS in men. Overall, fat indices had a greater influence on BMD in women, while lean indices were more positively associated with bone strength in men. Considering different fat indices, ALM was more strongly associated with BMD in women, whereas hand grip strength played a greater role in men. Thus, maintaining both muscle mass and strength is crucial for preserving bone mass.

Effect of omega-3 fatty acids supplementation on muscle mass, fat mass, and visceral fat of hemodialysis patients; A randomized clinical trial.

Several studies demonstrated the benefits of omega-3 fatty acids supplementation in chronic kidney disease (CKD) patients. The objective of this study was to investigate the effect of omega-3 fatty acids supplementation in body composition, specifically on the lean body mass and fat mass in hemodialysis patients. In this randomized, double-blind, placebo-controlled clinical trial, a total of 120 end-stage renal disease (ESRD) patients were randomly allocated into two groups. The intervention group has taken three grams of omega-3 fatty acids daily while the placebo group received three grams of medium chain triglycerides (MCT) as a placebo for a total of 2months. The changes in the body mass index (BMI) and body composition (fat mass, muscle, and visceral fat) were assessed at baseline and following the intervention. No significant difference was found in the mean of BMI, FAT, muscle, and visceral fat in the intervention group compared to the control group after the intervention. After two months of omega-3 fatty acid supplementation, the study found no statistically significant impact of omega-3 fatty acids supplementation on various indices of body composition. The effect of ω-3 supplementation in reducing visceral fat was close to significant (p=0.08). This study suggests that there is currently inadequate evidence to support the effect of omega-3 fatty acid supplementation in improving anthropometric measurements in patients with CKD, except a partial effect on visceral fat. Further large-scale and long-term clinical trials are needed to confirm the present results.

Prognostic impact of adipose tissue loss at 1month after surgery in patients with gastric cancer.

The postoperative impact of short-term changes in skeletal muscle loss (SML) and adipose tissue loss (ATL) on treatment outcomes is unclear in patients with gastric cancer (GC). We investigate the role of SML and ATL at 1month after surgery in determining postoperative survival and recurrence rates in patients with GC. We analyzed 540 patients with GC and assessed their skeletal muscle mass, visceral fat mass, and subcutaneous fat mass using computed tomography scans preoperatively and 1month postoperatively. Patients were categorized into high and low groups based on their levels of SML, visceral ATL (v-ATL), and subcutaneous ATL (s-ATL). Additionally, they were classified into three groups (high ATL, intermediate ATL, and low ATL) based on their v-ATL and s-ATL measurements. Patients with higher v-ATL and s-ATL had lower overall survival (OS) and recurrence-free survival (RFS) rates. High ATL was an independent prognostic factor for decreased OS (hazard ratio [HR] 2.27; 95% confidence interval [CI] 1.16-4.42; and P=0.02) and RFS (HR 2.51; 95% CI 1.34-4.71; and P=0.004) rates. A reduction in adipose tissue volume shortly after surgery (1month) could potentially indicate an increased risk of recurrence and mortality in patients with GC.

Sarcopenia risk in U.S. younger adults: the impact of physical activity intensity and occupational engagement-insights from a cross-sectional NHANES study.

This study aimed to investigate the associations between physical activity (PA) intensity, occupational PA engagement, and sarcopenia in younger adults. Data from the National Health and Nutrition Examination Survey (NHANES) (from 2011 to 2018) were used for the study. PA data were extracted for the Global Physical Activity Questionnaire, and the ratio of limb muscle mass (ALM) to body mass index (BMI) was used to determine sarcopenia. Multiple logistic regression was performed, and dose-response curves were drawn to evaluate the associations. Of the 8802 adults aged 20 to 59 years, 770 (8.7%) were identified as having sarcopenia. Compared to those in the reference group, the participants in the "low", "moderate", and "high" total METs groups had lower risks of sarcopenia (low: OR = 0.730, 95% CI = 0.583; 0.915; moderate: OR = 0.643, 95% CI = 0.485; 0.853; high: OR = 0.560, 95% CI = 0.457; 0.687). The risk of sarcopenia decreased in the high-intensity recreational PA group; however, such a significant association was observed only in the high-intensity occupational PA group. The relationship between total METs and sarcopenia showed a nonlinear U-shaped trend. A greater intensity of PA is associated with a lower risk of sarcopenia among younger adults, regardless of whether moderate or vigorous PA is performed. Moreover, recreational PA may particularly advantageously contrast with occupational PA in lowering the risk of sarcopenia.

The impact of Life's Essentials 8 on sarcopenia prevalence among adults in the United States.

Sarcopenia is closely associated with cardiovascular disease. We aimed to examine the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health (CVH), with the presence of sarcopenia among US adults. This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey in 2005-2006 and 2011-2018, and included adults aged 20 years or older. LE8 score was measured according to American Heart Association definitions. Sarcopenia was measured according to the National Institutes of Health definition, the ratio of appendicular skeletal muscle mass (ASM) to body mass index (BMI). Multivariable logistic and restricted cubic spline models were used to assess the associations between LE8 and sarcopenia. Among the 11,078 participants, 1021 (9.22 %) were diagnosed with sarcopenia. After adjusting for potential confounders, higher LE8, health behavior and health factors scores were associated with reduced odds ratios (OR) of sarcopenia (OR for per 10 scores increase in LE8, 0.65; 95 % CI 0.61-0.70; OR for per 10 scores increase in health behaviors score, 0.90; 95 % CI 0.84-0.97; OR for per 10 scores increase in health factors score, 0.67; 95 % CI 0.63-0.71). A non-linear dose-response relationship was observed between LE8 scores, health factors scores, and sarcopenia. The inversed association between LE8 score and sarcopenia was significantly stronger among males and participants with a high school education or above. LE8 was negatively associated with the prevalence of sarcopenia in a nonlinear fashion. Promoting adherence to optimal CVH levels may benefit to reduce the risk of sarcopenia.

The Effects of Agaro-Oligosaccharides Produced by Marine Bacteria (Rheinheimera sp. (HY)) Possessing Agarose-Degrading Enzymes on Myotube Function

Agarase and its metabolites are reported to have applications in a variety of fields, but there have been few studies of the effects of agaro-oligosaccharide hydrolysate on muscle function. In this study, we analyzed the functionality of agarase and its metabolites in bacteria isolated from seawater. A bacterium with agar-degrading activity was isolated from Shimabara, Nagasaki, Japan. Through 16S rRNA sequence alignment, it was identified as being closely related to Rheinheimera sp. WMF-1 and was provisionally named Rheinheimera sp. (HY). Crude enzymes derived from this bacterium demonstrated an ability to hydrolyze various polysaccharides, including agar, agarose, and starch, with the highest specificity observed for agarose. The optimum pH and temperature were pH 10 and 50 °C. A glycoside bond specificity analysis of enzymatic activity indicated the cleavage of the α-linkage. Next, we investigated the functional effects of agaro-oligosaccharides on C2C12 myotubes. Treatment with 10–30 kDa oligosaccharides significantly increased the hypertrophy rate, diameter, and expression of myosin heavy-chain genes in C2C12 myotubes. These results indicate that the agaro-oligosaccharides produced by the enzymes identified in this study improve muscle mass, suggesting their potential contribution to muscle function.

Treatment with tofacitinib attenuates muscle loss through myogenin activation in the collagen-induced arthritis.

Sarcopenia is a muscle disease characterized by reduction of muscle strength and muscle mass. In RA, 25.9 to 43.3% of the patients present sarcopenia. The loss of muscle mass observed in RA patients occurs either by activation of catabolic pathways or by inhibition of anabolic pathways. Despite having a list of drugs capable of treating RA inflammation, their effect on muscle is unclear. Our objective was to evaluate the tofacitinib effect on the muscle mass of collagen-induced arthritis (CIA) mice. CIA was induced in male DBA/1J mice by subcutaneous injection of Type 2 Collagen plus Freund Adjuvant. Animals were randomized into 3 groups: CIA + tofacitinib; CIA + vehicle; and healthy controls. Treatment was administered twice a day, between days 18 and 45 after induction. Clinical score, edema, and body weight were evaluated during the experimental period. After euthanasia, tibiotarsal joints were collected for assessment of disease histopathological score, and tibialis anterior (TA) and gastrocnemius (GA) muscles were weighed to assess muscle mass. Muscle atrophy was evaluated by measurement of TA myofiber cross-sectional area (CSA). Protein expression was evaluated by western blot using GA homogenates. Serum inflammatory markers were evaluated by ELISA. Statistical analysis included ANOVA followed by Tukey's or with Kruskal-Wallis. The statistical difference was assumed for p < 0.05. Tofacitinib treatment decreased arthritis severity by reducing clinical score, and hind paw edema in comparison with the vehicle group. Tofacitinib showed weight gain, higher TA and GA weights, and increased CSA compared to the vehicle group. On day 45, Tofacitinib presented increased muscle strength compared to the vehicle group, however, no difference was found in muscle fatigue. Pax7 expression was unchanged, while MyoD expression showed an increasing trend, and myogenin expression was significantly increased in Tofacitinib compared to vehicle and control groups. The treatment didn't modify Murf-1 expression. Tofacitinib mice showed decreased serum levels of TNF and increased IL-6 serum levels. Tofacitinib attenuated muscle loss in arthritic mice, increased muscle weight and muscle CSA. Activation of satellite cell regeneration, based on the increased expression of myogenin, is a potential mechanism involved in tofacitinib action against muscle loss.

Tanshinone IIA alleviates inflammation-induced skeletal muscle atrophy by regulating mitochondrial dysfunction.

Skeletal muscle atrophy, characterized by loss of muscle mass and function, is often linked to systemic inflammation. Tanshinone IIA (Tan IIA), a major active constituent of Salvia miltiorrhiza, has anti-inflammatory and antioxidant properties. However, the effect of Tan IIA on inflammation-induced skeletal muscle atrophy remains unclear. Here, a mice model of the inflammatory muscle atrophy was established using lipopolysaccharide (LPS). Tan IIA intervention significantly increased muscle mass and strength, improved muscle fiber size, and maintained the integrity of skeletal muscle mitochondrial morphology in LPS-treated mice. Myotubes derived from myosatellite cells (MUSCs) were exposed to LPS in vitro. Tan IIA treatment inhibited LPS-induced muscle protein degradation and increased myotube diameter. Notably, Tan IIA attenuated LPS-induced inflammatory response and hyperactive mitophagy both in vivo and in vitro. In addition, Tan IIA treatment effectively diminished oxidative stress, inhibited the accumulation of mitochondrial reactive oxygen species (mtROS), and attenuated mitochondrial fission in LPS-treated myotubes. Reducing mtROS production helped to inhibit LPS-induced excessive mitophagy and myotubes atrophy. Together, our results reveal that Tan IIA can protect against inflammation-induced skeletal muscle atrophy by regulating mitochondrial dysfunction, presenting innovative potential therapeutics for skeletal muscle atrophy.

Association between sarcopenia and the foot-ankle function in type 2 diabetic foot ulcer.

The diabetic foot (DF) ulcer is the severe complication of type 2 diabetes mellitus (T2DM). Sarcopenia is characterized as the loss of muscle mass and strength, resulting in the increased risk of fracture and physical disability. Sarcopenia may affect the foot-ankle function in DF ulcer patients, compromise the quality of life. The aim was to clarify the effect of sarcopenia on foot-ankle function in patients with DF ulcer. In total of 108 T2DM patients with DF ulcer were enrolled. Based on the examination of muscle mass by dual energy X-ray absorptiometry (DXA) and grip strength and 5x sit-to-stand test, the DF patients were divided into sarcopenia and non-sarcopenia groups. The severity of DF ulcer was evaluated by Wagner classification. The foot-ankle function was evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score. DF patients with sarcopenia showed advanced age, lower BMI, longer duration of T2DM, and more severe Wagner classification, reduced appendicular skeletal muscle mass index (ASMI), grip strength, transcutaneous oxygenpressure (TcPO2) and prolonged time of 5X sit-to-stand test. The stratified comparison analysis indicated that severity of sarcopenia and DF ulcer, reduced TcPO2, and grip strength were aggravated with the impaired foot-ankle function (P < 0.05). Multivariate Logistic analysis showed that age, TcPO2, and severe sarcopenia were risk factors deteriorating the foot-ankle function. The sarcopenia is a key risk factor of decreasing foot-ankle function in patients with DF ulcer. Thus, the prevention of muscle mass and strength loss could be considered as part of comprehensive therapy for DF ulcer.