Muscle Volume Research Articles

Changes in Supraspinatus Muscle Volume and Fat Fraction After Arthroscopic Rotator Cuff Repair at Minimum Follow-up of 5 Years

Changes in Supraspinatus Muscle Volume and Fat Fraction After Arthroscopic Rotator Cuff Repair at Minimum Follow-up of 5 Years

Heat exposure promotes sarcopenia via gut microbiota-derived metabolites.

The unprecedented rise in global ambient temperatures in the last decade has significantly impacted human health, yet how heat exposure affects the development of sarcopenia remains enigmatic. Here, we demonstrate that chronic heat exposure induces skeletal muscle volume loss, leading to muscle strength and functional decline in mice. The microbiota composition of heat-exposed mice was analyzed using 16S ribosomal DNA analysis. Liquid chromatography-mass spectrometry (LC-MS) was used to explore the effects of heat exposure on the blood metabolome and to further analyze the correlation between blood metabolism and gut microbiota. Transplantation of microbiota from heat-exposed mice to germ-free mice was sufficient to increase adverse effects on skeletal muscle function in the host. Mechanistically, using an untargeted metabolomics strategy, we reveal that altered gut microbiota due to high temperatures is associated with elevated serum levels of homocitrulline. Homocitrulline causes mitochondrial dysfunction in myocytes by exacerbating ferroptosis levels. And Nrf2 activator (Oltipraz) supplementation alleviates muscle atrophy and dysfunction induced by heat exposure. Our findings reveal the detrimental effects of heat exposure on muscle function and provide new strategies for treating sarcopenia.

Decreased volume of rectus femoris and iliocapsularis in patients with femoroacetabular impingement syndrome after primary hip arthroscopy

Purpose(1) to investigate the consecutive changes in hip muscle volume in patients with femoroacetabular impingement syndrome (FAIS) during the initial postoperative period, and (2) to determine the potential effect of the early changes in hip muscle volume on clinical outcomes.MethodsData between March 2021 and March 2022 was reviewed. Patients diagnosed with FAIS based on clinical symptoms and radiographic findings, and undergoing hip arthroscopic treatment were included. Exclusion criteria were incomplete MRI data, prior history of hip surgery, and concomitant hip conditions including hip osteoarthritis with a Tönnis grade > 1, avascular necrosis, Legg-Calvé-Perthes disease, osteoid osteoma, synovial chondromatosis, pigmented villonodular synovitis, and developmental dysplasia of the hip (DDH). MRI was performed preoperatively and 3, 6, 12-month postoperatively. Cross-sectional area (CSA) of hip muscles including rectus femoris (RF), iliocapsularis (IC), iliopsoas (IP), gluteus medius/minimus complex (G-med/min), and gluteus maximus (G-max) were collected on MRI. The CSA was corrected by body surface area (BSA). Preoperative and a minimum of 2-year postoperative patient-reported outcome (PRO) scores including Visual Analog pain Scale (VAS), modified Harris Hip Score (mHHS), and international Hip Outcome Tool, 12-component form (iHOT-12) were collected. A multivariate linear regression model was built to determine the influence of the potential factors on postoperative PROs.ResultsA total of 76 patients were included in the study. Compared to the preoperative level, decreased volume of RF and G-max, and increased IC/RF ratio were observed at postoperative 3 months (all with P < .05). Both G-med/min and G-max presented decreased volume at postoperative 6 months (all with P < .05). G-med/min presented decreased volume (P = .001) at postoperative 12 months. Changes in RF at postoperative 3 months and 12 months were positively related to improvement of iHOT-12 (Beta = 0.371, P = .012 and Beta = 0.330, P = .026, respectively). Changes in IC at postoperative 6-month was positively related to improvement of mHHS (Beta = 0.367, P = .027) and iHOT-12 (Beta = 0.315, P = .044).ConclusionDuring the initial first year following arthroscopic treatment for FAIS, decreased volume of the RF and gluteal muscles was observed. Early changes in volume of RF and IC were positively correlated to the improvement of minimum 2-year PROs.Level of evidenceLevel IV; case series.

Effects of Atezolizumab plus Bevacizumab on Skeletal Muscle Volume and Cardiac Function in Patients with Hepatocellular Carcinoma

Introduction: Pharmacological treatment of unresectable hepatocellular carcinoma (uHCC) includes sorafenib and lenvatinib, a tyrosine kinase inhibitor, which are linked to low serum levels of carnitine and reduced skeletal muscle volume. Nowadays, atezolizumab plus bevacizumab (Atezo/Bev) combination therapy is recommended as the first-line treatment for patients with uHCC. However, the association with decreased muscle mass or cardiac function is unknown. Therefore, this study aimed to evaluate the effects of Atezo/Bev on skeletal muscle volume and cardiac function in patients with uHCC. Methods: This retrospective study included 55 adult Japanese patients with chronic liver diseases and uHCC treated with Atezo/Bev. Patients were divided into three groups according to age: middle, preold, and old. Serum levels of carnitine and cardiac function were measured before and after 3 weeks of treatment. The psoas muscle index (PMI) was measured before and after 6 weeks of treatment. Results: After treatment, the global longitudinal strain was significantly lower in the old group, whereas the PMI and ejection fraction were significantly lower in the preold and old groups. However, no significant difference in serum levels of total carnitine and those fractions with treatment in each group was found. Cardiac function decreased in the preold and old groups. Conclusion: When treating patients with uHCC by Atezo/Bev, caution should be taken in preold and old patients because they are vulnerable to decreased skeletal muscle mass and deterioration of cardiac function. Strength training and regular monitoring of cardiac function are encouraged in these groups.

Combination of nusinersen and rehabilitation using hybrid assistive limb for type 3 spinal muscular atrophy

AbstractAn antisense oligonucleotide drug nusinersen can improve motor function of spinal muscular atrophy (SMA) patients. The Hybrid Assistive Limb (HAL) is a wearable robot assisting the wearers' movements in real time. Gait rehabilitation using HAL is useful for SMA. However, the efficacy of combined treatment has never been reported before. We have investigated the efficacy of combining both therapies. A 21‐year‐old man, genetically diagnosed with type 3 SMA, was treated by combining nusinersen and five sessions of gait rehabilitation using HAL over 2 years. Hammersmith Functional Motor Scale‐Expanded (HFMSE) score improved by 12 points after treatment. Electrophysiological parameters of the tibial nerves improved. Muscle volume also increased by 8% at 39 months. The combined therapy resulted in a good clinical outcome. This may be due to promotion of nerve regeneration and recovery of muscle volume by a synergy of nusinersen and motor learning correctly guided by HAL.

Muscular Hypertrophy and its Relation to Strength Performance: A Physics-Based Analysis of Conceptual Inaccuracies

ABSTRACT The interchangeable use of terms such as muscle mass, volume, cross-sectional area, and thickness in discussions on the physiology of muscle hypertrophy has led to misconceptions in research and practice. This review aims to highlight the improperness of this approach and highlights the overlooked parameter of muscular density (MD). The hypothesis is that muscle density acts as a mediator, leading to inevitable muscle enlargement in long-term strength training. It is proposed that research in muscular adaptations to training should implement measures of MD to complement measurements of muscle size. This article aims to refine the understanding of muscular adaptations and optimize training strategies for athletes and fitness enthusiasts.

A mouse model of volumetric muscle loss and therapeutic scaffold implantation.

Skeletal myofibers naturally regenerate after damage; however, impaired muscle function can result in cases when a prominent portion of skeletal muscle mass is lost, for example, following traumatic muscle injury. Volumetric muscle loss can be modeled in mice using a surgical model of muscle ablation to study the pathology of volumetric muscle loss and to test experimental treatments, such as the implantation of acellular scaffolds, which promote de novo myogenesis and angiogenesis. Here we provide step-by-step instructions to perform full-thickness surgical ablation, using biopsy punches, and to remove a large volume of the tibialis anterior muscle of the lower limb in mice. This procedure results in a reduction in muscle mass and limited regeneration capacity; the approach is easy to reproduce and can also be applied to larger animal models. For therapeutic applications, we further explain how to implant bioscaffolds into the ablated muscle site. With adequate training and practice, the surgical procedure can be performed within 30 min.

Enhanced Myogenic Differentiation of Human Adipose‐Derived Stem Cells via Integration of 3D Bioprinting and In Situ Shear‐Based Blade Coating

AbstractConventional treatments for volumetric muscle loss (VML) encounter limitations, such as donor site constraints and exploration of tissue engineering methods. Here, the fabrication of human adipose stem cell (hASC)‐laden cell constructs are proposed using a 3D bioprinting technique supported by blade casting. This process induces mechanotransduction to activate stem cell activities, including proliferation and myogenic differentiation. The printing conditions are optimized by assessing the effects of various process parameters on mechanotransduction signaling pathways. Notably, blade‐assisted bioprinting under carefully selected parameters enhanced the in vitro myogenic activity of the fabricated hASC constructs. Moreover, in vivo evaluation in mice with VML defects demonstrate that shear‐induced bioconstructs effectively restored lost functionalities and muscle volume compared to those of normally bioprinted cell constructs. The results show the potential of integrating bioprinting with hASC‐based therapies to enhance muscle regeneration and functional recovery, offering a meaningful platform for future tissue engineering approaches for VML treatment.

Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?

Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1-based therapies are under development. For future development of GLP-1-based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future.

CT-based body composition analysis and pulmonary fat attenuation volume as biomarkers to predict overall survival in patients with non-specific interstitial pneumonia

BackgroundNon-specific interstitial pneumonia (NSIP) is an interstitial lung disease that can result in end-stage fibrosis. We investigated the influence of body composition and pulmonary fat attenuation volume (CTpfav) on overall survival (OS) in NSIP patients.MethodsIn this retrospective single-center study, 71 NSIP patients with a median age of 65 years (interquartile range 21.5), 39 females (55%), who had a computed tomography from August 2009 to February 2018, were included, of whom 38 (54%) died during follow-up. Body composition analysis was performed using an open-source nnU-Net-based framework. Features were combined into: Sarcopenia (muscle/bone); Fat (total adipose tissue/bone); Myosteatosis (inter-/intra-muscular adipose tissue/total adipose tissue); Mediastinal (mediastinal adipose tissue/bone); and Pulmonary fat index (CTpfav/lung volume). Kaplan–Meier analysis with a log-rank test and multivariate Cox regression were used for survival analyses.ResultsPatients with a higher (> median) Sarcopenia and lower (< median) Mediastinal Fat index had a significantly better survival probability (2-year survival rate: 83% versus 71% for high versus low Sarcopenia index, p = 0.023; 83% versus 72% for low versus high Mediastinal fat index, p = 0.006). In univariate analysis, individuals with a higher Pulmonary fat index exhibited significantly worse survival probability (2-year survival rate: 61% versus 94% for high versus low, p = 0.003). Additionally, it was an independent risk predictor for death (hazard ratio 2.37, 95% confidence interval 1.03–5.48, p = 0.043).ConclusionFully automated body composition analysis offers interesting perspectives in patients with NSIP. Pulmonary fat index was an independent predictor of OS.Relevance statementThe Pulmonary fat index is an independent predictor of OS in patients with NSIP and demonstrates the potential of fully automated, deep-learning-driven body composition analysis as a biomarker for prognosis estimation.Key PointsThis is the first study assessing the potential of CT-based body composition analysis in patients with non-specific interstitial pneumonia (NSIP).A single-center analysis of 71 patients with board-certified diagnosis of NSIP is presentedIndices related to muscle, mediastinal fat, and pulmonary fat attenuation volume were significantly associated with survival at univariate analysis.CT pulmonary fat attenuation volume, normalized by lung volume, resulted as an independent predictor for death.Graphical

Is decreased psoas volume a risk factor for hip fracture? A comparative study of patients with and without hip fractures using the exact matching technique

IntroductionSarcopenia is linked to increased fall and hip fracture risk. However, studies often overlook comprehensively controlling for age, sex, bone mineral density (BMD), and body mass index (BMI). Our study aimed to determine if sarcopenia, determined by evaluating the psoas muscle volume, is an independent risk factor for hip fractures. We employed a methodological approach that includes the exact matching technique. MethodsIn this cross-sectional comparative study, we compared the data of patients who sustained hip fractures between 2015 and 2021 with those of a control group from a health screening center in a single center. The study included 545 patients with hip fractures and 1292 without fractures. We collected data on demographics, BMD determined using dual-energy X-ray absorptiometry, and abdominal and pelvic computed tomography (APCT) scans for psoas muscle volume analysis. ResultsThe analysis after exact matching of 266 pairs revealed that psoas volume/height2 was the most significant and dominant risk factor among the evaluated indices. Multivariate logistic regression analysis, adjusting for age, sex, BMI, and BMD, identified height or height2-adjusted psoas muscle volume as an independent risk factor for hip fractures (p = 0.042 and p = 0.002, respectively). Age, female sex, lower BMI, and lower BMD were associated with an increased risk of hip fractures. ConclusionDecreased psoas muscle volume adjusted for patient height independently predicts hip fracture risk. Psoas volume assessment via APCT is a practical tool for identifying at-risk individuals, emphasizing the necessity of including sarcopenia in hip fracture risk assessments.

Exploration of the triceps surae muscle in ambulatory children with cerebral palsy using instrumented measurements of stiffness and diffusion tensor magnetic resonance imaging for muscle architecture

BackgroundMusculoskeletal alterations causing reduced range of motion of the ankle joint are common in children with cerebral palsy (CP). Objective measurements of passive joint resistance and three-dimensional skeletal muscle volume and muscle architecture can lead to a comprehensive understanding of which factors influence joint range of motion.Research questionTo investigate the relation between the passive dorsiflexion of the ankle joint, biomechanical contributing factors to the passive joint resistance, and muscular architectural properties of the triceps surae muscle in children with CP.MethodsIn this cross-sectional observational study, 14 children with spastic CP (bilateral: 5, unilateral: 9, Gross Motor Function Classification System (GMFCS) level I:11, II:3) naïve to intramuscular tone reducing treatment, and 14 TD children were included. The passive dorsiflexion of the ankle was measured with a goniometer. Passive joint resistance and related parameters were estimated based on a biomechanical model and measurements using a motorized device, the Neuroflexor. Three-dimensional muscle architecture was quantified with diffusion tensor magnetic resonance imaging (DT-MRI).ResultsIn the CP group, the median [min, max] passive dorsiflexion was decreased in the most affected leg (MAL) compared to the less affected leg (LAL) (2.5° [-25°, 20°] vs. 12.5° [5°, 30°], p = 0.001). The stiffness coefficient (Nm/rad) in the MAL was significantly higher in children with CP compared to TD children (7.10 [3.39, 62.00] vs. 2.82 [1.24, 10.46], p = 0.015). Muscle architecture properties did not differ between CP and TD, except for pennation angle in the medial gastrocnemius (MG) of the MAL (CP 17.64° (2.29) vs. TD 21.46° (3.20), p = 0.017). The stiffness coefficient, in the MAL, correlated negatively to passive dorsiflexion (rs=-0.638) and pennation angle in medial gastrocnemius (rs=-0.964), and the non-linear coefficient (Non-linear 1) correlated negatively to the fascicle length of the medial gastrocnemius (rs=-0.857).ConclusionThis study shows that stiffness of the plantarflexors is related to decreased passive dorsiflexion of the ankle and muscle structure of the MG in high-functioning children with spastic CP. Assessments of how dynamic components as well as microscopic muscle alterations contribute to joint stiffness in the plantarflexors in individuals with CP are warranted.Trial registrationRetrospectively registered in ClinicalTrials.gov, NCT05447299. Observational study. Study start: 2019-01-15, register date: 2022-07-01.

Body composition and muscle composition phenotypes in patients on waitlist and shortly after liver transplant – results from a pilot study

BackgroundSarcopenia is common in end-stage liver disease and negatively impacts patients awaiting or undergoing liver transplantation (LT). Magnetic resonance imaging (MRI) may be used to measure body composition and sarcopenia. We aimed to evaluate the feasibility of MRI-based LT body composition profiling, describe waitlist body composition, and assess the natural rate of change in body composition while on the waitlist and post-LT.MethodsThis prospective pilot study recruited adults listed for LT at an urban, tertiary care facility. Eighteen participants were scanned at time of waitlisting and 15 had follow-up MRIs (waitlist and/or post-LT). An 8-min MRI was used to measure body composition (AMRA® Researcher) including thigh fat-free muscle volume (FFMV) and fat infiltration (MFI), visceral (VAT) and abdominal subcutaneous (ASAT) adipose tissue volumes, and liver fat. A sex- and BMI invariant FFMV z-score (z-FFMV) was calculated, and muscle composition (MC) phenotypes were defined using the muscle assessment score (consisting of the FFMV z-score and sex-adjusted MFI). Rate of body composition change was calculated using mixed-effect modelling and is presented as rate per 30 days.ResultsAt time of waitlisting, 73% of the 18 participants had high MFI and 39% had the adverse MC (low FFMV z-score and high MFI) phenotype. Seven participants received an LT. Post-LT serial MRIs, at a median of 147 days apart within the first 200 days post-LT, demonstrated increased z-FFMV 0.22 SDs/(30 days) (p = 0.002), VAT 0.23 (p < 0.001), and ASAT 0.52 (p = 0.001) L/(30 days), but no change in MFI (p = 0.200) nor liver fat (p = 0.232).ConclusionMRI-based body composition profiling is feasible in LT patients and shortly after LT. This can be amended to routine clinical scans and may help in early identification of patients who may benefit from interventions to improve body composition. In addition, body composition changes significantly over time after LT.

9208 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, &amp; B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

7896 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, &amp; B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

7138 Testosterone Modulation of Muscle Transcriptome Profile During Intensive Lifestyle Intervention in Older Men With Obesity and Hypogonadism

Abstract Disclosure: V. Viola: None. T. Samanta: None. M. Duremdes Nava: None. A. Celli: None. R.C. Villareal: None. N.H. Nguyen: None. G. Colleluori: None. Y. Barnouin: None. N. Napoli: None. C. Qualls: None. B.A. Kaipparettu: None. D.T. Villareal: None. Background: We reported that testosterone replacement added to lifestyle therapy can mitigate weight loss-induced reduction of muscle mass and bone mineral density (BMD) in older men with obesity and hypogonadism (Barnouin et al., J Clin Endocrinol Metab, 2021). Objective: To investigate the molecular mechanisms underlying the mitigation of muscle and BMD loss in response to testosterone replacement therapy during intensive lifestyle intervention in this at-risk population. Materials and Methods: Among the 83 older (≥ 65 y) men with obesity (BMI ≥ 30 kg/m2) and hypogonadism (early AM testosterone persistently &amp;lt;300 ng/dl) associated with frailty (PPT score ≤ 31) who were randomized into 26-week lifestyle therapy plus testosterone (LT+Test) or placebo (LT+Pbo), 38 underwent serial muscle biopsies for the muscle transcriptomics substudy. Results: Despite a similar 9% weight loss, lean body mass and thigh muscle volume decreased less in LT+Test than LT+Pbo (both -2% vs -4%, respectively; p=0.04). Hip BMD was preserved in LT+Test compared with LT+Pbo (0.4% vs -1.1%; p=0.03). Muscle strength increased similarly in LT+Test and LT+Pbo (23% vs 24%; p=0.95). Total testosterone increased more in LT+Test than LT+Pbo (133% vs 32%; p=0.01). Based on Next Generation Sequencing, of the 39,160 and 39,115 genes detected in LT+Test and LT+Pbo, respectively, 151 genes were differentially expressed (DEGs) in LT+Test and 114 in LT+Pbo group. Gene Ontology enrichment analyses revealed that in the LT+Test group, just four muscle-related terms (muscle organ development, muscle organ morphogenesis, regulation of skeletal muscle contraction, muscle atrophy) were downregulated, and one term (muscle system process) was upregulated while in the LT+Pbo, nine terms related to muscle (muscle system process, muscle tissue development, muscle organ development, skeletal muscle tissue development, skeletal muscle organ development, skeletal muscle cell differentiation, muscle organ morphogenesis, response to stimuli involved in regulation of muscle adaptation, muscle atrophy), and one term related to bone (bone mineralization involved in bone maturation) were downregulated. Notably, muscle system process was upregulated in the LT+Test but downregulated in the LT+Pbo. The RT-PCR analyses showed that LT+Test resulted in a higher expression of MYOD1 (p=0.02) and WNT4 (p= 0.08), key genes involved in muscle and bone metabolism, respectively, compared to LT+Pbo. Furthermore, we observed significantly higher mRNA expression of MYBPH (p=0.01), SCN3B (p=0.02), and DSC2 (p=0.01), genes involved in the muscle system process, in response to LT+Test compared to LT+Pbo. Conclusion: The addition of testosterone replacement to lifestyle therapy mitigates the weight loss-induced reduction of muscle mass and BMD via countering the weight loss-induced downregulation of genes involved in muscle and bone anabolism. Presentation: 6/2/2024

9208 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, &amp; B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

Multiscale hamstring muscle adaptations following 9 weeks of eccentric training.

Eccentric training, such as Nordic hamstring exercise (NHE) training, is commonly used as a preventive measure for hamstring strains. Eccentric training is believed to induce lengthening of muscle fascicles and to be associated with the addition of sarcomeres in series within muscle fibers. However, the difficulty in measuring sarcomere adaptation in human muscles has severely limited information about the precise mechanisms of adaptation. This study addressed this limitation by measuring the multiscale hamstring muscle adaptations in response to 9 weeks of NHE training and 3 weeks of detraining. Twelve participants completed 9 weeks of supervised NHE training, followed by a 3-week detraining period. We assessed biceps femoris long-head (BFlh) muscle fascicle length, sarcomere length, and serial sarcomere number in the central and distal regions of the muscle. Additionally, we measured muscle volume and eccentric strength at baseline, post-training, and post-detraining. NHE training over 9 weeks induced significant architectural and strength adaptations in the BFlh muscle. Fascicle length increased by 19% in the central muscle region and 33% in the distal muscle region. NHE also induced increases in serial sarcomere number (25% in the central region and 49% in the distal region). BFlh muscle volume increased by 8%, and knee flexion strength increased by 40% with training. Following 3 weeks of detraining, fascicle length decreased by 12% in the central region and 16% in the distal region along with reductions in serial sarcomere number. Nine weeks of NHE training produced substantial, region-specific increases in BFlh muscle fascicle length, muscle volume, and force generation. The direct measurement of sarcomere lengths revealed that the increased fascicle length was accompanied by the addition of sarcomeres in series within the muscle fascicles.

Poor muscle health and cardiometabolic risks associated with antidepressant treatment.

This study aims to investigate whether antidepressant users display differences in fat distribution and muscle composition relative to non-users and to explore risk factors for developing cardiovascular disease (CVD) and type 2 diabetes. The study used quantitative adipose and muscle tissue measures derived from magnetic resonance imaging data from UK Biobank (N = 40,174). Fat distribution and muscle composition of selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepressant (TCA) users were compared with sex-, age-, and BMI-matched control individuals. Cox regression models were used to test for increased risk of developing CVD and type 2 diabetes. SSRI users had more visceral fat, smaller muscle volume, and higher muscle fat infiltration compared with matched control individuals. Female users showed a larger increase in BMI over time compared with male users. However, male users displayed an unhealthier body composition profile. Male SSRI users also had an increased risk of developing CVD. Both male and female TCA users showed lower muscle volume and an increased risk of developing type 2 diabetes. Adverse changes in body composition of antidepressant users are not captured by tracking the body weight or the BMI of the patients. These changes may lead to a worsened cardiometabolic risk profile.

Anatomical insights into fish terrestrial locomotion: A study of barred mudskipper (Periophthalmus argentilineatus) fins based on μCT 3D reconstructions.

Mudskippers are a group of extant ray-finned fishes with an amphibious lifestyle and serve as exemplars for understanding the evolution of amphibious capabilities in teleosts. A comprehensive anatomical profile of both the soft and hard tissues within their propulsive fins is essential for advancing our understanding of terrestrial locomotor adaptations in fish. Despite the ecological significance of mudskippers, detailed data on their musculoskeletal anatomy remains limited. In the present research, we utilized contrast-enhanced high-resolution microcomputed tomography (μCT) imaging to investigate the barred mudskipper, Periophthalmus argentilineatus. This technique enabled detailed reconstruction and quantification of the morphological details of the pectoral, pelvic, and caudal fins of this terrestrial mudskipper, facilitating comparison with its aquatic relatives. Our findings reveal that P. argentilineatus has undergone complex musculoskeletal adaptations for terrestrial movement, including an increase in muscle complexity and muscle volume, as well as the development of specialized structures like aponeuroses for pectoral fin extension. Skeletal modifications are also evident, with features such as a reinforced shoulder-pelvic joint and thickened fin rays. These evolutionary modifications suggest biomechanically advanced fins capable of overcoming the gravitational challenges of terrestrial habitats, indicating a strong selective advantage for these features in land-based environments. The unique musculoskeletal modifications in the fins of mudskippers like P. argentilineatus, compared with their aquatic counterparts, mark a critical evolutionary shift toward terrestrial adaptations. This study not only sheds light on the specific anatomical changes facilitating this transition but also offers broader insights into the early evolutionary mechanisms of terrestrial locomotion, potentially mirroring the transformative journey from aquatic to terrestrial life in the lineage leading to tetrapods.