Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"Body composition derangements in lung cancer patients treated with first-line pembrolizumab: A multicentre observational study","authors":"Ilaria Trestini, Lorenzo Belluomini, Alessandra Dodi, Marco Sposito, Alberto Caldart, Dzenete Kadrija, Luca Pasqualin, Silvia Teresa Riva, Ilaria Mariangela Scaglione, Daniela Tregnago, Alice Avancini, Jessica Insolda, Linda Confortini, Miriam Casali, Jessica Menis, Emanuele Vita, Marco Cintoni, Marco Todesco, Gianluca Milanese, Isabella Sperduti, Mirko D'Onofrio, Marco Infante, Marcello Tiseo, Maria Cristina Mele, Giampaolo Tortora, Michele Milella, Emilio Bria, Sara Pilotto","doi":"10.1002/jcsm.13568","DOIUrl":"https://doi.org/10.1002/jcsm.13568","url":null,"abstract":"While immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non-small-cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long-lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre-treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first-line pembrolizumab monotherapy for advanced NSCLC.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"109 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on 'AWGC2023 Cachexia Consensus as a Valuable Tool for Predicting Prognosis and Burden in Chinese Patients With Cancer' by Xie et al.","authors":"Xiaosong Li, Xiping Shen, Ji Wu","doi":"10.1002/jcsm.13622","DOIUrl":"https://doi.org/10.1002/jcsm.13622","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on ‘Change in Physical Activity and Its Association With Decline in Kidney Function: A UK Biobank-Based Cohort Study’ by Liu et al.","authors":"Zhenzhi Qin, Yan Xu","doi":"10.1002/jcsm.13623","DOIUrl":"https://doi.org/10.1002/jcsm.13623","url":null,"abstract":"<p>We read with great interest the recent article by Welsh et al. titled ‘Change in physical activity and its association with decline in kidney function: A UK Biobank-based cohort study’ in <i>Journal of Cachexia, Sarcopenia and Muscle</i> [<span>1</span>]. The study finds that increased physical activity may protect kidney function, as suggested by the modest yet significant associations observed in large-scale analyses using eGFRCysC measurements. However, we note several biases in the use of the Cox proportional hazards (CoxPH) model that the authors did not address.</p>\u0000<p>The established criteria may result in mixed censoring outcomes, that is, right-censoring and interval-censoring events [<span>2, 3</span>]. Events of kidney function diagnosed through medical records could result in interval-censoring if they occurred between follow-up visits, and right-censoring for diagnosed between the end of follow-up and the time of data analysis. The CoxPH model primarily handles right-censored data. In contrast, the accelerated failure time (AFT) model is often preferred for scenarios involving various types of censored data [<span>4</span>]. The AFT model can effectively handle left-censored, right-censored and interval-censored data by appropriately adjusting the likelihood function [<span>5</span>]. By using the ‘survival’ and ‘icenReg’ packages, mixed censored data can be fitted and analysed, and event times can be estimated [<span>6</span>].</p>\u0000<p>Moreover, the CoxPH model requires the proportional hazards assumption, meaning that covariate effects are constant over time [<span>7</span>]. If this assumption is violated, the model may not provide unbiased estimates of the coefficients, and the predictions may not be reliable. The authors should utilize Schoenfeld residuals or alternative methods to evaluate the proportional hazards assumption for the association between covariates and the risk of kidney function. Schoenfeld residuals are calculated as the differences between the observed and expected values of covariates at each failure time [<span>8</span>]. If the residuals exhibit a systematic change over time, it suggests that the effect of the covariate may be time-dependent. When the proportional hazards assumption does not hold, authors should use a stratified Cox model, a Cox model with time-varying effects, or an AFT model instead of the standard CoxPH model [<span>4, 9</span>].</p>\u0000<p>In conclusion, we believe that a re-evaluation considering the potential impact of censoring events and the proportional hazards assumption is necessary. Further research is anticipated to provide more empirical data and clearer insights into this field.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"108 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on 'Effects of Sarcopenia and Frailty on Postoperative Recovery in Elderly Patients: A Prospective Cohort Study' by Guo et al.","authors":"Hongrui Chen, Zening Huang, Qinqi Yu, Bin Sun, Chen Hua, Xiaoxi Lin","doi":"10.1002/jcsm.13625","DOIUrl":"https://doi.org/10.1002/jcsm.13625","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on ‘Myosteatosis and Muscle Loss Impact Liver Transplant Outcomes in Male Patients With Hepatocellular Carcinoma’ by Lu et al.","authors":"Aikaterini Kamiliou, Vasileios Lekakis, George Xynos, Evangelos Cholongitas","doi":"10.1002/jcsm.13620","DOIUrl":"https://doi.org/10.1002/jcsm.13620","url":null,"abstract":"<p>We read with great interest the article by Lu et al. [<span>1</span>] regarding the impact of myosteatosis on post–liver transplantation (LT) outcome in males transplanted for hepatocellular carcinoma (HCC). The authors reported a relatively low prevalence of myosteatosis (27.8% in males) using a gender-based definition (i.e., muscle attenuation less than 37.5 HU at the third lumbar vertebra of cross-sectional CT image for men). However, in our recently published meta-analysis [<span>2</span>] including 10 studies with 3316 HCC patients, the overall pooled prevalence of myosteatosis was estimated as high as 50% (95% confidence interval [CI] 35%–65%) [<span>2</span>]. This discrepancy could be attributed to the fact that Lu et al. [<span>1</span>] included mainly chronic hepatitis B–associated HCC patients, although all patients were Asians. Indeed, our meta-analysis showed that the prevalence of myosteatosis is significantly lower in Asian HCC patients, compared to the non-Asian HCC patients (pooled prevalence 45% vs. 69%, respectively, <i>p</i> = 0.02), whereas viral-associated HCC patients have significantly less frequently myosteatosis, compared to those with fatty or alcoholic liver disease–associated HCC (pooled prevalence 49% vs. 65% vs. 86%, respectively, <i>p</i> &lt; 0.001). Interestingly, the authors [<span>1</span>] concluded that myosteatosis was not associated with post-LT outcome in females, although they did not provide which cutoff was used for definition of myosteatosis in this subgroup, although no clear explanation was given for this finding. In addition, they found no association between myosteatosis and hepatic encephalopathy although our meta-analysis [<span>3</span>] showed that cirrhotic patients with myosteatosis, compared to those without myosteatosis, have more frequently a previous history of hepatic encephalopathy (32% vs. 15%, <i>p</i> = 0.04) possibly related with the reduction of skeletal muscle capacity to remove ammonia. Finally, it would be interesting if the authors evaluated the impact of diabetes mellitus, which is an known factor associated with myosteatosis and poor prognosis after LT [<span>3, 4</span>], as well as if they compared the post-LT outcome of HCC patients with sarcopenia and myosteatosis/isolated myosteatosis versus those with isolated sarcopenia, as recent studies have shown that myosteatosis may be a more important factor, compared to sarcopenia, in the pre-LT setting of patients without HCC [<span>5</span>].</p>\u0000<p>Nevertheless, Lu et al. [<span>1</span>] confirmed the predictive role of myosteatosis in HCC patients not only in the pre-LT setting [<span>2</span>] but also in the post-LT outcome [<span>1</span>], indicating the importance of including assessment of myosteatosis in the process for LT evaluation. However, their results [<span>1</span>] need validation in non-Asian populations, in which the aetiology of liver disease is more frequently metabolic and alcohol-related HCC.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"8 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on ‘Neuromuscular Impairment at Different Stages of Human Sarcopenia’ by Sarto et al.","authors":"Ross A. Jones, Abdullah Ramadan, Shahd Qutifan, Thomas H. Gillingwater","doi":"10.1002/jcsm.13624","DOIUrl":"https://doi.org/10.1002/jcsm.13624","url":null,"abstract":"&lt;p&gt;We read with interest the paper entitled ‘Neuromuscular impairment at different stages of human sarcopenia’ by Sarto et al. [&lt;span&gt;1&lt;/span&gt;], which has used a variety of assessment approaches to innovatively investigate neuromuscular impairment in older human subjects. This study undoubtedly represents an important contribution to our understanding of the impact of age and sarcopenia on the human neuromuscular system, for which we wish to congratulate and thank the authors.&lt;/p&gt;\u0000&lt;p&gt;Although the authors have presented a lot of important new data, they state in their conclusions that ‘an altered innervation profile and NMJ instability are prominent features of the ageing of the neuromuscular system’. This is based on the claim that an increase in neural cell adhesion molecule-positive fibres is evidence of ‘increased muscle denervation’. We would like to raise caution against such a conclusion when based on the type of indirect data presented by Sarto et al. [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;The term ‘muscle denervation’ refers to a specific process whereby the nerve supply (innervation) of a muscle fibre, derived from a lower motor neuron input, is removed or lost. For this term to be accurate, therefore, it requires evidence showing that lower motor neuron inputs at the NMJ are removed or lost. We would politely suggest that an increase in neural cell adhesion molecule-positive fibres is not such evidence. Rather, anatomical and morphological studies of the NMJ are required to be able to draw such conclusions.&lt;/p&gt;\u0000&lt;p&gt;Sarto et al. [&lt;span&gt;1&lt;/span&gt;] point out in their paper that morphological evidence for NMJ disruption, and hence muscle denervation, is present in rodent models of ageing [&lt;span&gt;2&lt;/span&gt;] and use this to support their claims in humans. However, whilst technically challenging, comparable morphological studies of NMJs in young and old humans have been performed, showing that, in stark contrast to rodent models, NMJs remain structurally intact over the normal human lifespan [&lt;span&gt;3&lt;/span&gt;]. Such species-specific differences are perhaps not surprising given the inherent differences that exist in NMJ structure and stability between rodents and humans [&lt;span&gt;4, 5&lt;/span&gt;]. As such, the strongest &lt;i&gt;direct&lt;/i&gt; evidence available to date suggests that motor neuron inputs at the NMJ are not removed or lost with increasing age in humans. This in no way precludes the possibility that age- and/or sarcopenia-related changes, such as those reported by Sarto et al., [&lt;span&gt;1&lt;/span&gt;] are occurring in muscle that mimic denervation-induced changes. Rather, it questions the premise that such changes are occurring due to a loss of innervation resulting from structural breakdown of the NMJ.&lt;/p&gt;\u0000&lt;p&gt;The use of indirect measurements to draw conclusions about NMJ status and muscle denervation is not an issue solely restricted to Sarto et al.'s paper [&lt;span&gt;1&lt;/span&gt;], and we by no means wish to single out this important study in this regard (indeed, we strongly welc","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"44 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on ‘Survey on the Knowledge and Practices in Anorexia of Aging Diagnosis and Management in Japan’ by Takagi et al.","authors":"Ying Cui","doi":"10.1002/jcsm.13626","DOIUrl":"https://doi.org/10.1002/jcsm.13626","url":null,"abstract":"<p>I have read with great interest the article published in the <i>Journal of Cachexia, Sarcopenia and Muscle</i> on the knowledge and practices in anorexia of ageing (AA) diagnosis and management in Japan [<span>1</span>]. The study provides valuable insights into the current state of AA management among healthcare professionals in Japan, emphasizing the critical role of continuing education. While the article is well written and contributes meaningfully to the field, I believe there are several areas where constructive suggestions could further enhance the interpretation and application of the results.</p>\u0000<p>From a statistical perspective, the study has some limitations that merit consideration. The use of descriptive statistics and chi-square tests to compare differences between the education and non-education groups is commendable. However, incorporating multivariable regression models could make the analysis even more insightful, as these models would effectively control for potential confounding factors such as participants' work experience, institutional resources and overall attitudes towards elderly care. Additionally, examining interaction effects could significantly enhance the persuasiveness of the study's findings. Education may impact the management of AA differently across various professions, regions or institutions. Considering these interaction effects within the statistical models would provide a deeper understanding of how these factors collectively influence the results [<span>2</span>].</p>\u0000<p>To address the challenges highlighted by this study, I propose a multidisciplinary approach involving community health initiatives. A coordinated effort that includes healthcare providers, community health workers, social workers and government officials could create a more supportive environment for managing AA. For example, community-based nutrition education programmes could be developed to reach a broader audience, including those outside academic settings. Additionally, leveraging the role of community health workers to monitor and manage AA in older adults could enhance early detection and intervention [<span>3</span>], particularly in underserved areas.</p>\u0000<p>In conclusion, while the article offers valuable contributions to understanding AA management in Japan, our suggestions aim to make an already excellent article even better. I look forward to seeing continued efforts from healthcare professionals, volunteers, government officials and social workers to create a healthier and more supportive environment for older adults.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"1 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-Term Multicomponent Exercise Impact on Muscle Function and Structure in Hospitalized Older at Risk of Acute Sarcopenia.","authors":"Mikel L Sáez de Asteasu,Nicolás Martínez-Velilla,Fabricio Zambom-Ferraresi,Yesenia García-Alonso,Arkaitz Galbete,Robinson Ramírez-Vélez,Eduardo L Cadore,Mikel Izquierdo","doi":"10.1002/jcsm.13602","DOIUrl":"https://doi.org/10.1002/jcsm.13602","url":null,"abstract":"BACKGROUNDHospitalization exacerbates sarcopenia and physical dysfunction in older adults. Whether tailored inpatient exercise prevents acute sarcopenia is unknown. This study aimed to examine the effect of a multicomponent exercise programme on muscle and physical function in hospitalized older adults. We hypothesized that participation in a brief tailored exercise regimen (i.e., 3-5 days) would attenuate muscle function and structure changes compared with usual hospital care alone.METHODSThis randomized clinical trial with blinded outcome assessment was conducted from May 2018 to April 2021 at Hospital Universitario de Navarra, Spain. Participants were 130 patients aged 75 years and older admitted to an acute care geriatric unit. Patients were randomized to a tailored 3- to 5-day exercise programme (n = 64) or usual hospital care (control, n = 66) consisting of physical therapy if needed. The coprimary endpoints were between-group differences in changes in short physical performance battery (SPPB) score and usual gait velocity from hospital admission to discharge. Secondary endpoints included changes in rectus femoris echo intensity, cross-sectional area, thickness and subcutaneous and intramuscular fat by ultrasound.RESULTSAmong 130 randomized patients (mean [SD] age, 87.7 [4.6] years; 57 [44%] women), the exercise group increased their mean SPPB score by 0.98 points (95% CI, 0.28-1.69 points) and gait velocity by 0.09 m/s (95% CI, 0.03-0.15 m/s) more than controls (both p < 0.01). No between-group differences were observed in any ultrasound muscle outcomes. There were no study-related adverse events.CONCLUSIONSThree to 5 days of tailored multicomponent exercise provided functional benefits but did not alter muscle or fat architecture compared with usual hospital care alone among vulnerable older patients. Brief exercise may help prevent acute sarcopenia during hospitalization.TRIAL REGISTRATIONClinicalTrials.gov identifier: NCT04600453.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"2020 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body Composition and Progression of Biopsy-Proven Non-Alcoholic Fatty Liver Disease in Patients With Obesity.","authors":"Qianyi Wan, Xingzhu Liu, Jinghao Xu, Rui Zhao, Shiqin Yang, Jianrong Feng, Zhan Cao, Jingru Li, Xiaopeng He, Haiou Chen, Jinbao Ye, Haiyang Chen, Yi Chen","doi":"10.1002/jcsm.13605","DOIUrl":"https://doi.org/10.1002/jcsm.13605","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a significant risk factor for the progression of non-alcoholic fatty liver disease (NAFLD). However, a convenient and efficacious non-invasive test for monitoring NAFLD progression in patients with obesity is currently lacking. This study aims to investigate the associations between CT-based body composition and the progression of biopsy-proven NAFLD in patients with obesity.</p><p><strong>Methods: </strong>Liver biopsy was conducted in patients with obesity, and the progression of NAFLD was evaluated by the NAFLD activity score (NAS). Body composition was assessed through abdominal computed tomography (CT) scans.</p><p><strong>Results: </strong>A total of 602 patients with an average age of 31.65 (±9.33) years old were included, comprising 217 male patients and 385 female patients. The wall skeletal muscle index (SMI), total SMI, and visceral fat index (VFI) were positively correlated with NAS in both male and female patients. Multivariate regression analysis demonstrated significant associations between high liver steatosis and wall SMI (HR: 1.60, 95% CI: 1.12 to 2.30), total SMI (HR: 1.50, 95% CI: 1.02 to 2.08), VSI (HR: 2.16, 95% CI: 1.48 to 3.14), visceral fat to muscle ratio (HR: 1.51, 95% CI: 1.05 to 2.18), and visceral to subcutaneous fat ratio (HR: 1.51, 95% CI: 1.07 to 2.12). Non-alcoholic steatohepatitis (NASH) was significantly associated with wall SMI (HR: 1.52, 95% CI: 1.06 to 2.19) and VSI (HR: 1.50, 95% CI: 1.03 to 2.17). Liver fibrosis ≥ F2 was significantly associated with psoas muscle index (HR: 0.64, 95% CI: 0.44 to 0.93) and psoas skeletal muscle density (HR: 0.61, 95% CI: 0.41 to 0.89).</p><p><strong>Conclusions: </strong>Our study suggested that certain CT-based body composition indicators, notably high VFI, were significantly associated with the progression of NAFLD in patients with obesity. Great attentions and timely managements should be given to these patients with body composition characteristics associated with the risk of NAFLD progression.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of CILP2 Improves Glucose Metabolism and Mitochondrial Dysfunction in Sarcopenia via the Wnt Signalling Pathway.","authors":"Zhibo Deng, Chao Song, Long Chen, Rongsheng Zhang, Linhai Yang, Peng Zhang, Yu Xiu, Yibin Su, Fenqi Luo, Jun Luo, Hanhao Dai, Jie Xu","doi":"10.1002/jcsm.13597","DOIUrl":"https://doi.org/10.1002/jcsm.13597","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Skeletal muscle is the primary organ involved in insulin-mediated glucose metabolism. Elevated levels of CILP2 are a significant indicator of impaired glucose tolerance and are predominantly expressed in skeletal muscle. It remains unclear whether CILP2 contributes to age-related muscle atrophy through regulating the glucose homeostasis and insulin sensitivity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Initially, the expression levels of CILP2 were assessed in elderly mice and patients with sarcopenia. Lentiviral vectors were used to induce either silencing or overexpression of CILP2 in C2C12 myoblast cells. The effects of CILP2 on proliferation, myogenic differentiation, insulin sensitivity and glucose uptake were evaluated using immunofluorescence, western blotting, real-time quantitative polymerase chain reaction, RNA sequencing, glucose uptake experiments, dual-luciferase reporter assays and co-immunoprecipitation (CO-IP). An adeno-associated virus-9 containing a muscle-specific promoter was injected into SAMP8 senile mice to observe the efficacy of CILP2 knockout.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We found that there was more CLIP2 expressed in the skeletal muscle of ageing mice (+1.1-fold, p &lt; 0.01) and in patients with sarcopenia (+2.5-fold, p &lt; 0.01) compared to the control group. Following the overexpression of CILP2, Ki67 (-65%, p &lt; 0.01), PCNA (-32%, p &lt; 0.05), MyoD1 (-89%, p &lt; 0.001), MyoG (-31%, p &lt; 0.05) and MyHC (-85%, p &lt; 0.001), which indicate proliferation and differentiation potential, were significantly reduced. In contrast, MuRF-1 (+59%, p &lt; 0.05), atrogin-1 (+43%, p &lt; 0.05) and myostatin (+31%, p &lt; 0.05), the markers of muscular atrophy, were significantly increased. Overexpression of CILP2 decreased insulin sensitivity, glucose uptake (-18%, p &lt; 0.001), GLUT4 translocation to the membrane and the maximum respiratory capacity of mitochondria. Canonical Wnt signalling was identified through RNA sequencing as a potential pathway for CILP2 regulation in C2C12, and Wnt3a was confirmed as an interacting protein of CILP2 in the CO-IP assay. The addition of recombinant Wnt3a protein reversed the inhibitory effects on myogenesis and glucose metabolism caused by CILP2 overexpression. Conversely, CILP2 knockdown promoted myogenesis and glucose metabolism. CILP2 knockdown improved muscle atrophy in mice, characterized by significant increases in time to exhaustion (+42%, p &lt; 0.001), grip strength (+19%, p &lt; 0.01), muscle mass (+15%, p &lt; 0.001) and mean muscle cross-sectional area (+37%, p &lt; 0.01). CILP2 knockdown enhanced glycogen synthesis (+83%, p &lt; 0.001) and the regeneration of oxidative and glycolytic muscle fibres in SAMP8 ageing mice via the Wnt/β-catenin signalling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our results indicate that CILP2 interacts with Wnt3a to suppress the Wnt/β-catenin signalling pathway and its downstream cascade, leading to impaired insulin sensitivity and glucose metabolism in skelet","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}