Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"Cachexia causes time-dependent activation of the inflammasome in the liver","authors":"Rodrigo Xavier das Neves,&nbsp;Alex S. Yamashita,&nbsp;Daniela M.R. Riccardi,&nbsp;Julia K?hn-Gaone,&nbsp;Rodolfo G. Camargo,&nbsp;Nelson I. Neto,&nbsp;Daniela Caetano,&nbsp;Silvio P. Gomes,&nbsp;Felipe H. Santos,&nbsp;Joanna D.C.C. Lima,&nbsp;Miguel L. Batista Jr,&nbsp;José Cesar Rosa-Neto,&nbsp;Paulo Sérgio Martins De Alcantara,&nbsp;Linda F. Maximiano,&nbsp;José P. Otoch,&nbsp;Giorgio Trinchieri,&nbsp;Janina E.E. Tirnitz-Parker,&nbsp;Marília Seelaender","doi":"10.1002/jcsm.13236","DOIUrl":"https://doi.org/10.1002/jcsm.13236","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cachexia is a wasting syndrome associated with systemic inflammation and metabolic disruption. Detection of the early signs of the disease may contribute to the effective attenuation of associated symptoms. Despite playing a central role in the control of metabolism and inflammation, the liver has received little attention in cachexia. We previously described relevant disruption of metabolic pathways in the organ in an animal model of cachexia, and herein, we adopt the same model to investigate temporal onset of inflammation in the liver. The aim was thus to study inflammation in rodent liver in the well-characterized cachexia model of Walker 256 carcinosarcoma and, in addition, to describe inflammatory alterations in the liver of one cachectic colon cancer patient, as compared to one control and one weight-stable cancer patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Colon cancer patients (one weight stable [WSC] and one cachectic [CC]) and one patient undergoing surgery for cholelithiasis (control, <i>n</i> = 1) were enrolled in the study, after obtainment of fully informed consent. Eight-week-old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 × 10⁷ cells in 1.0 mL; tumour-bearing [T]; or phosphate-buffered saline—controls [C]). The liver was excised on Days 0 (<i>n</i> = 5), 7 (<i>n</i> = 5) and 14 (<i>n</i> = 5) after tumour cell injection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In rodent cachexia, we found progressively higher numbers of CD68⁺ myeloid cells in the liver along cancer-cachexia development. Similar findings are described for CC, whose liver showed infiltration of the same cell type, compared with both WSC and control patient organs. In advanced rodent cachexia, hepatic phosphorylated c-Jun N-terminal kinase protein content and the inflammasome pathway protein expression were increased in relation to baseline (<i>P</i> &lt; 0.05). These changes were accompanied by augmented expression of the active interleukin-1β (IL-1β) form (<i>P</i> &lt; 0.05 for both circulating and hepatic content).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results show that cancer cachexia is associated with an increase in the number of myeloid cells in rodent and human liver and with modulation of hepatic inflammasome pathway. The latter contributes to the aggravation of systemic inflammation, through increased release of IL-1β.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1621-1630"},"PeriodicalIF":8.9,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6107268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcopenia and health-related quality of life: A systematic review and meta-analysis","authors":"Charlotte Beaudart,&nbsp;Céline Demonceau,&nbsp;Jean-Yves Reginster,&nbsp;Médéa Locquet,&nbsp;Matteo Cesari,&nbsp;Alfonso J. Cruz Jentoft,&nbsp;Olivier Bruyère","doi":"10.1002/jcsm.13243","DOIUrl":"https://doi.org/10.1002/jcsm.13243","url":null,"abstract":"<p>The decrease of physical abilities and functional decline that can be caused by musculoskeletal conditions such as sarcopenia, can lead to higher levels of dependency and disability. Therefore, it may influence patient reported outcome measures (PROM), such as the health-related quality of life (HRQoL). The purpose of this systematic review and meta-analysis is to provide a comprehensive overview of the relationship between sarcopenia and HRQoL. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed throughout the whole process of this work. A protocol was previously published on PROSPERO. The electronic databases MEDLINE, Scopus, Allied and Complementary Medicine (AMED), EMB Review – ACP Journal Club, EBM Review - Cochrane Central of Register of Controlled Trials and APA PsychInfo were searched until October 2022 for observational studies reporting a HRQoL assessment in both sarcopenic and non-sarcopenic individuals. Study selection and data extraction were carried out by two independent researchers. Meta-analysis was performed using a random effect model, reporting an overall standardized mean difference (SMD) and its 95% confidence interval (CI) between sarcopenic and non-sarcopenic individuals. Study quality was measured using the Newcastle-Ottawa Scale and the strength of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. The search strategy identified 3725 references from which 43 observational studies were eligible and included in this meta-synthesis study. A significantly lower HRQoL was observed for sarcopenic individuals compared with non-sarcopenic ones (SMD −0.76; 95% CI −0.95; −0.57). Significant heterogeneity was associated with the model (<i>I</i>² = 93%, <i>Q</i> test <i>P</i>-value &lt;0.01). Subgroup analysis showed a higher effect size when using the specific questionnaire SarQoL compared with generic questionnaires (SMD −1.09; 95% CI −1.44; −0.74 with the SarQoL versus −0.49; 95% CI −0.63; −0.36 with generic tools; <i>P</i>-value for interaction &lt;0.01). A greater difference of HRQoL between sarcopenic and non-sarcopenic was found for individuals residing in care homes compared with community-dwelling individuals (<i>P</i>-value for interaction &lt;0.001). No differences were found between age groups, diagnostic techniques, and continents/regions. The level of evidence was rated as moderate using the GRADE assessment. This systematic review and meta-analysis combining 43 observational studies shows that HRQoL is significantly reduced in sarcopenic patients. The use of disease-specific HRQoL instruments may better discriminate sarcopenic patients with respect to their quality of life.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 3","pages":"1228-1243"},"PeriodicalIF":8.9,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6123636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence for inefficient contraction and abnormal mitochondrial activity in sarcopenia using magnetic resonance spectroscopy","authors":"Mary C. Stephenson,&nbsp;Jamie X.M. Ho,&nbsp;Eugenia Migliavacca,&nbsp;Maria Kalimeri,&nbsp;Neerja Karnani,&nbsp;Subhasis Banerji,&nbsp;John J. Totman,&nbsp;Jerome N. Feige,&nbsp;Reshma A. Merchant,&nbsp;Stacey K.H. Tay","doi":"10.1002/jcsm.13220","DOIUrl":"https://doi.org/10.1002/jcsm.13220","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mitochondrial dysfunction has been implicated in sarcopenia. ³¹P magnetic resonance spectroscopy (MRS) enables non-invasive measurement of adenosine triphosphate (ATP) synthesis rates to probe mitochondrial function. Here, we assessed muscle energetics in older sarcopenic and non-sarcopenic men and compared with muscle biopsy-derived markers of mitochondrial function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty Chinese men with sarcopenia (SARC, age = 73.1 ± 4.1 years) and 19 healthy aged and sex-matched controls (CON, age = 70.3 ± 4.2 years) underwent assessment of strength, physical performance, and magnetic resonance imaging. Concentrations of phosphocreatine (PCr), ATP and inorganic phosphate (Pi) as well as muscle pH were measured at rest and during an interleaved rest–exercise protocol to probe muscle mitochondrial function. Results were compared to biopsy-derived mitochondrial complex activity and expression to understand underlying metabolic perturbations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Despite matched muscle contractile power (strength/cross-sectional area), the ATP contractile cost was higher in SARC compared with CON (low-intensity exercise: 1.06 ± 0.59 vs. 0.57 ± 0.22, moderate: 0.93 ± 0.43 vs. 0.58 ± 0.68, high: 0.70 ± 0.57 vs. 0.43 ± 0.51 mmol L⁻¹ min⁻¹ bar⁻¹ cm⁻², <i>P</i> = 0.003, &lt;0.0001 and &lt;0.0001, respectively). Post-exercise mitochondrial oxidative synthesis rates (a marker of mitochondrial function) tended to be longer in SARC but did not reach significance (17.3 ± 6.4 vs. 14.6 ± 6.5 mmol L⁻¹ min⁻¹, <i>P</i> = 0.2). However, relative increases in end-exercise ADP in SARC (31.8 ± 9.9 vs. 24.0 ± 7.3 mmol L⁻¹, <i>P</i> = 0.008) may have been a compensatory mechanism. Mitochondrial complex activity was found to be associated with exercise-induced drops in PCr [citrate synthetase activity (CS), Spearman correlation rho = −0.42, <i>P</i> = 0.03] and end-exercise ADP (complex III, rho = −0.52, <i>P</i> = 0.01; CS rho = −0.45, <i>P</i> = 0.02; SDH rho = −0.45, <i>P</i> = 0.03), with CS also being strongly associated with the PCr recovery rate following low intensity exercise (rho = −0.47, <i>P</i> = 0.02), and the cost of contraction at high intensity (rho = −0.54, <i>P</i> = 0.02). Interestingly, at high intensity, the fractional contribution of oxidative phosphorylation to exercise was correlated with activity in complex II (rho = 0.5, <i>P</i> = 0.03), CS (rho = 0.47, <i>P</i> = 0.02) and SDH (rho = 0.46, <i>P</i> = 0.03), linking increased mitochondrial complex activity with ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 3","pages":"1482-1494"},"PeriodicalIF":8.9,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13220","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6092273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milk protects against sarcopenic obesity due to increase in the genus Akkermansia in faeces of db/db mice","authors":"Takuro Okamura,&nbsp;Masahide Hamaguchi,&nbsp;Hanako Nakajima,&nbsp;Nobuko Kitagawa,&nbsp;Saori Majima,&nbsp;Takafumi Senmaru,&nbsp;Hiroshi Okada,&nbsp;Emi Ushigome,&nbsp;Naoko Nakanishi,&nbsp;Ryoichi Sasano,&nbsp;Michiaki Fukui","doi":"10.1002/jcsm.13245","DOIUrl":"https://doi.org/10.1002/jcsm.13245","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenic obesity, a combination of sarcopenia and obesity, is a pathological feature of type 2 diabetes. Several human studies have shown that milk is useful in the prevention of sarcopenia. This study was aimed at clarifying the effect of milk on the prevention of sarcopenic obesity in <i>db/db</i> mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A randomized and investigator-blinded study was conducted using male <i>db/db</i> mice. Eight-week-old <i>db/db</i> mice were housed for 8 weeks and fed milk (100 μL/day) using a sonde. The faecal microbiota transplantation (FMT) group received antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Milk administration to <i>db/db</i> mice increased grip strength (Milk−: 164.2 ± 4.7 g, Milk+: 230.2 ± 56.0 g, <i>P</i> = 0.017), muscle mass (soleus muscle, Milk−: 164.2 ± 4.7 mg, Milk+: 230.2 ± 56.0 mg, <i>P</i> &lt; 0.001; plantaris muscle, Milk−: 13.3 ± 1.2 mg, Milk+: 16.0 ± 1.7 mg, <i>P</i> &lt; 0.001) and decreased visceral fat mass (Milk−: 2.39 ± 0.08 g, Milk+: 1.98 ± 0.04 mg, <i>P</i> &lt; 0.001), resulting in a significant increase in physical activity (light: <i>P</i> = 0.013, dark: <i>P</i> = 0.034). FMT from mice fed milk not only improved sarcopenic obesity but also significantly improved glucose intolerance. Microarray analysis of gene expression in the small intestine revealed that the expression of amino acid absorption transporter genes, namely, <i>SIc7a5</i> (<i>P</i> = 0.010), <i>SIc7a1</i> (<i>P</i> = 0.015), <i>Ppp1r15a</i> (<i>P</i> = 0.041) and <i>SIc7a11</i> (<i>P</i> = 0.029), was elevated in mice fed milk. In 16S rRNA sequencing of gut microbiota, the genus <i>Akkermansia</i> was increased in both the mice fed milk and the FMT group from the mice fed milk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings of this study suggest that besides increasing the intake of nutrients, such as amino acids, milk consumption also changes the intestinal environment, which might contribute to the mechanism of milk-induced improvement of sarcopenic obesity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 3","pages":"1395-1409"},"PeriodicalIF":8.9,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6064465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of S-pindolol in mouse pancreatic and lung cancer cachexia models","authors":"Jochen Springer,&nbsp;Queralt Jové,&nbsp;Edson Alves de Lima Junior,&nbsp;Natalia álvarez Ladrón,&nbsp;Francisco Javier López-Soriano,&nbsp;Silvia Busquets,&nbsp;Josep M. Argiles,&nbsp;Daniel L. Marks","doi":"10.1002/jcsm.13249","DOIUrl":"https://doi.org/10.1002/jcsm.13249","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>It is known that S-pindolol attenuates muscle loss in animal models of cancer cachexia and sarcopenia. In cancer cachexia, it also significantly reduced mortality and improved cardiac function, which is strongly compromised in cachectic animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we tested 3 mg/kg/day of S-pindolol in two murine cancer cachexia models: pancreatic cancer cachexia (KPC) and Lewis lung carcinoma (LLC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment of mice with 3 mg/kg/day of S-pindolol in KPC or LLC cancer cachexia models significantly attenuated the loss of body weight, including lean mass and muscle weights, leading to improved grip strength compared with placebo-treated mice. In the KPC model, treated mice lost less than half of the total weight lost by placebo (−0.9 ± 1.0 vs. −2.2 ± 1.4 g for S-pindolol and placebo, respectively, <i>P</i> &lt; 0.05) and around a third of the lean mass lost by tumour-bearing controls (−0.4 ± 1.0 vs. −1.5 ± 1.5 g for S-pindolol and placebo, respectively, <i>P</i> &lt; 0.05), whereas loss of fat mass was similar. In the LLC model, the gastrocnemius weight was higher in sham (108 ± 16 mg) and S-pindolol tumour-bearing (94 ± 15 mg) mice than that in placebo (83 ± 12 mg), whereas the soleus weight was only significantly higher in the S-pindolol-treated group (7.9 ± 1.7 mg) than that in placebo (6.5 ± 0.9). Grip strength was significantly improved by S-pindolol treatment (110.8 ± 16.2 vs. 93.9 ± 17.1 g for S-pindolol and placebo, respectively). A higher grip strength was observed in all groups; whereas S-pindolol-treated mice improved by 32.7 ± 18.5 g, tumour-bearing mice only show minimal improvements (7.3 ± 19.4 g, <i>P</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>S-pindolol is an important candidate for clinical development in the treatment of cancer cachexia that strongly attenuates loss of body weight and lean body mass. This was also seen in the weight of individual muscles and resulted in higher grip strength.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 3","pages":"1244-1248"},"PeriodicalIF":8.9,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6061103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty acid amides as potential circulating biomarkers for sarcopenia","authors":"Ye An Kim,&nbsp;Seung Hun Lee,&nbsp;Jung-Min Koh,&nbsp;Seung-hyun Kwon,&nbsp;Young Lee,&nbsp;Han Jin Cho,&nbsp;Hanjun Kim,&nbsp;Su Jung Kim,&nbsp;Ji Hyun Lee,&nbsp;Hyun Ju Yoo,&nbsp;Je Hyun Seo","doi":"10.1002/jcsm.13244","DOIUrl":"https://doi.org/10.1002/jcsm.13244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age. Given that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detection are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform experimental studies using metabolomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Plasma metabolites from 142 elderly men, comprising a sarcopenia group and an age-matched control group, were measured using global metabolome profiling. Muscle and plasma samples from an aging mouse model of sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted metabolome profiling. Based on these experimental results, fatty acid amides were quantified from human plasma as well as human muscle tissues. The association of fatty acid amide levels with sarcopenia parameters was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Global metabolome profiling showed that fatty acid amide levels were significantly different in the plasma of elderly men with sarcopenia (all <i>P</i>s &lt; 0.01). Consistent with these results in human plasma, targeted metabolome profiling in an aging mouse model of sarcopenia showed decreased levels of fatty acid amides in plasma but not in muscle tissue. In addition, the levels of fatty acid amides increased in cell lysates during muscle cell differentiation. Targeted metabolome profiling in men showed decreased docosahexaenoic acid ethanolamide (DHA EA) levels in the plasma (<i>P</i> = 0.016) but not in the muscle of men with sarcopenia. DHA EA level was positively correlated with sarcopenia parameters such as skeletal muscle mass index (SMI) and handgrip strength (HGS) (<i>P</i> = 0.001, <i>P</i> = 0.001, respectively). The area under the receiver-operating characteristic curve (AUC) for DHA EA level ≤ 4.60 fmol/μL for sarcopenia was 0.618 (95% confidence interval [CI]: 0.532–0.698). DHA EA level ≤ 4.60 fmol/μL was associated with a significantly greater likelihood of sarcopenia (odds ratio [OR]: 2.11, 95% CI: 1.03–4.30), independent of HGS. The addition of DHA EA level to age and HGS significantly improved the AUC from 0.620 to 0.691 (<i>P</i> = 0.0497).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrated that fatty acid amides are potential circulating biomarkers in elderly men with sarcopenia. DHA EA, in particular, strongly related to muscle mass and strength, can be a key ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 3","pages":"1558-1568"},"PeriodicalIF":8.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6028409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impairment of aryl hydrocarbon receptor signalling promotes hepatic disorders in cancer cachexia","authors":"Adeline Dolly,&nbsp;Sarah A. P?tgens,&nbsp;Morgane M. Thibaut,&nbsp;Audrey M. Neyrinck,&nbsp;Gabriela S. de Castro,&nbsp;Chloé Galbert,&nbsp;Camille Lefevre,&nbsp;Elisabeth Wyart,&nbsp;Silvio P. Gomes,&nbsp;Daniela C. Gon?alves,&nbsp;Nicolas Lanthier,&nbsp;Pamela Baldin,&nbsp;Joshua R. Huot,&nbsp;Andrea Bonetto,&nbsp;Marília Seelaender,&nbsp;Nathalie M. Delzenne,&nbsp;Harry Sokol,&nbsp;Laure B. Bindels","doi":"10.1002/jcsm.13246","DOIUrl":"https://doi.org/10.1002/jcsm.13246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The aryl hydrocarbon receptor (AHR) is expressed in the intestine and liver, where it has pleiotropic functions and target genes. This study aims to explore the potential implication of AHR in cancer cachexia, an inflammatory and metabolic syndrome contributing to cancer death. Specifically, we tested the hypothesis that targeting AHR can alleviate cachectic features, particularly through the gut–liver axis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>AHR pathways were explored in multiple tissues from four experimental mouse models of cancer cachexia (C26, BaF3, MC38 and APC^Min/+) and from non-cachectic mice (sham-injected mice and non-cachexia-inducing [NC26] tumour-bearing mice), as well as in liver biopsies from cancer patients. Cachectic mice were treated with an AHR agonist (6-formylindolo(3,2-<i>b</i>)carbazole [FICZ]) or an antibody neutralizing interleukin-6 (IL-6). Key mechanisms were validated in vitro on HepG2 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AHR activation, reflected by the expression of <i>Cyp1a1</i> and <i>Cyp1a2</i>, two major AHR target genes, was deeply reduced in all models (C26 and BaF3, <i>P</i> &lt; 0.001; MC38 and APC^Min/+, <i>P</i> &lt; 0.05) independently of anorexia. This reduction occurred early in the liver (<i>P</i> &lt; 0.001; before the onset of cachexia), compared to the ileum and skeletal muscle (<i>P</i> &lt; 0.01; pre-cachexia stage), and was intrinsically related to cachexia (C26 vs. NC26, <i>P</i> &lt; 0.001). We demonstrate a differential modulation of AHR activation in the liver (through the IL-6/hypoxia-inducing factor 1α pathway) compared to the ileum (attributed to the decreased levels of indolic AHR ligands, <i>P</i> &lt; 0.001), and the muscle. In cachectic mice, FICZ treatment reduced hepatic inflammation: expression of cytokines (<i>Ccl2</i>, <i>P</i> = 0.005; <i>Cxcl2</i>, <i>P</i> = 0.018; <i>Il1b</i>, <i>P</i> = 0.088) with similar trends at the protein levels, expression of genes involved in the acute-phase response (<i>Apcs</i>, <i>P</i> = 0.040; <i>Saa1</i>, <i>P</i> = 0.002; <i>Saa2</i>, <i>P</i> = 0.039; <i>Alb</i>, <i>P</i> = 0.003), macrophage activation (<i>Cd68</i>, <i>P</i> = 0.038) and extracellular matrix remodelling (<i>Fga</i>, <i>P</i> = 0.008; <i>Pcolce</i>, <i>P</i> = 0.025; <i>Timp1</i>, <i>P</i> = 0.003). We observed a decrease in blood glucose in cachectic mice (<i>P</i> &lt; 0.0001), which was also improved by FICZ treatment (<i>P</i> = 0.026) through hepatic transcriptional promotion of a key marker of gluconeogenesis, namely, <i>G6pc</i> (C26 vs. C26 + FICZ, <i>P</i> = 0.029). Strikingly, these ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 3","pages":"1569-1582"},"PeriodicalIF":8.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6077986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffusion-tensor magnetic resonance imaging captures increased skeletal muscle fibre diameters in Becker muscular dystrophy","authors":"Donnie Cameron,&nbsp;Tooba Abbassi-Daloii,&nbsp;Laura G.M. Heezen,&nbsp;Nienke M. van de Velde,&nbsp;Za?da Koeks,&nbsp;Thom T.J. Veeger,&nbsp;Melissa T. Hooijmans,&nbsp;Salma el Abdellaoui,&nbsp;Sjoerd G. van Duinen,&nbsp;Jan J.G.M. Verschuuren,&nbsp;Maaike van Putten,&nbsp;Annemieke Aartsma-Rus,&nbsp;Vered Raz,&nbsp;Pietro Spitali,&nbsp;Erik H. Niks,&nbsp;Hermien E. Kan","doi":"10.1002/jcsm.13242","DOIUrl":"https://doi.org/10.1002/jcsm.13242","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Becker muscular dystrophy (BMD) is an X-linked disorder characterized by slow, progressive muscle damage and muscle weakness. Hallmarks include fibre-size variation and replacement of skeletal muscle with fibrous and adipose tissues, after repeated cycles of regeneration. Muscle histology can detect these features, but the required biopsies are invasive, are difficult to repeat and capture only small muscle volumes. Diffusion-tensor magnetic resonance imaging (DT-MRI) is a potential non-invasive alternative that can calculate muscle fibre diameters when applied with the novel random permeable barrier model (RPBM). In this study, we assessed muscle fibre diameters using DT-MRI in BMD patients and healthy controls and compared these with histology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 13 BMD patients and 9 age-matched controls, who underwent water-fat MRI and DT-MRI at multiple diffusion times, allowing RPBM parameter estimation in the lower leg muscles. Tibialis anterior muscle biopsies were taken from the contralateral leg in 6 BMD patients who underwent DT-MRI and from an additional 32 BMD patients and 15 healthy controls. Laminin and Sirius-red stainings were performed to evaluate muscle fibre morphology and fibrosis. Twelve ambulant patients from the MRI cohort underwent the North Star ambulatory assessment, and 6-min walk, rise-from-floor and 10-m run/walk functional tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RPBM fibre diameter was significantly larger in BMD patients (<i>P</i> = 0.015): mean (SD) = 68.0 (25.3) μm versus 59.4 (19.2) μm in controls. Inter-muscle differences were also observed (<i>P</i> ≤ 0.002). Both inter- and intra-individual RPBM fibre diameter variability were similar between groups. Laminin staining agreed with the RPBM, showing larger median fibre diameters in patients than in controls: 72.5 (7.9) versus 63.2 (6.9) μm, <i>P</i> = 0.006. However, despite showing similar inter-individual variation, patients showed more intra-individual fibre diameter variability than controls—mean variance (SD) = 34.2 (7.9) versus 21.4 (6.9) μm, <i>P</i> &lt; 0.001—and larger fibrosis areas: median (interquartile range) = 21.7 (5.6)% versus 14.9 (3.4)%, <i>P</i> &lt; 0.001. Despite good overall agreement of RPBM and laminin fibre diameters, they were not associated in patients who underwent DT-MRI and muscle biopsy, perhaps due to lack of colocalization of DT-MRI with biopsy samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DT-MRI RPBM metrics agree with histolo","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 3","pages":"1546-1557"},"PeriodicalIF":8.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6043239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-translational regulation of muscle growth, muscle aging and sarcopenia","authors":"Qian Zhong,&nbsp;Kun Zheng,&nbsp;Wanmeng Li,&nbsp;Kang An,&nbsp;Yu Liu,&nbsp;Xina Xiao,&nbsp;Shan Hai,&nbsp;Biao Dong,&nbsp;Shuangqing Li,&nbsp;Zhenmei An,&nbsp;Lunzhi Dai","doi":"10.1002/jcsm.13241","DOIUrl":"https://doi.org/10.1002/jcsm.13241","url":null,"abstract":"<p>Skeletal muscle makes up 30–40% of the total body mass. It is of great significance in maintaining digestion, inhaling and exhaling, sustaining body posture, exercising, protecting joints and many other aspects. Moreover, muscle is also an important metabolic organ that helps to maintain the balance of sugar and fat. Defective skeletal muscle function not only limits the daily activities of the elderly but also increases the risk of disability, hospitalization and death, placing a huge burden on society and the healthcare system. Sarcopenia is a progressive decline in muscle mass, muscle strength and muscle function with age caused by environmental and genetic factors, such as the abnormal regulation of protein post-translational modifications (PTMs). To date, many studies have shown that numerous PTMs, such as phosphorylation, acetylation, ubiquitination, SUMOylation, glycosylation, glycation, methylation, S-nitrosylation, carbonylation and S-glutathionylation, are involved in the regulation of muscle health and diseases. This article systematically summarizes the post-translational regulation of muscle growth and muscle atrophy and helps to understand the pathophysiology of muscle aging and develop effective strategies for diagnosing, preventing and treating sarcopenia.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 3","pages":"1212-1227"},"PeriodicalIF":8.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6028418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathological correlations and fat replacement imaging patterns in recessive limb-girdle muscular dystrophy type 12","authors":"Bram De Wel,&nbsp;Lotte Huysmans,&nbsp;Christophe E. Depuydt,&nbsp;Veerle Goosens,&nbsp;Ronald Peeters,&nbsp;Filipa P. Santos,&nbsp;Dietmar R. Thal,&nbsp;Patrick Dupont,&nbsp;Frederik Maes,&nbsp;Kristl G. Claeys","doi":"10.1002/jcsm.13234","DOIUrl":"https://doi.org/10.1002/jcsm.13234","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite the widespread use of proton density fat fraction (PDFF) measurements with magnetic resonance imaging (MRI) to track disease progression in muscle disorders, it is still unclear how these findings relate to histopathological changes in muscle biopsies of patients with limb-girdle muscular dystrophy autosomal recessive type 12 (LGMDR12). Furthermore, although it is known that LGMDR12 leads to a selective muscle involvement distinct from other muscular dystrophies, the spatial distribution of fat replacement within these muscles is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 27 adult patients with LGMDR12 and 27 age-matched and sex-matched healthy controls and acquired 6-point Dixon images of the thighs and T1 and short tau inversion recovery (STIR) MR images of the whole body. In 16 patients and 15 controls, we performed three muscle biopsies, one in the semimembranosus, vastus lateralis, and rectus femoris muscles, which are severely, intermediately, and mildly affected in LGMDR12, respectively. We correlated the PDFF to the fat percentage measured on biopsies of the corresponding muscles, as well as to the Rochester histopathology grading scale.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In patients, we demonstrated a strong correlation of PDFF on MRI and muscle biopsy fat percentage for the semimembranosus (<i>r</i> = 0.85, <i>P</i> &lt; 0.001) and vastus lateralis (<i>r</i> = 0.68, <i>P</i> = 0.005). We found similar results for the correlation between PDFF and the Rochester histopathology grading scale. Out of the five patients with inflammatory changes on muscle biopsy, three showed STIR hyperintensities in the corresponding muscle on MRI. By modelling the PDFF on MRI for 18 thigh muscles from origin to insertion, we observed a significantly inhomogeneous proximo-distal distribution of fat replacement in all thigh muscles of patients with LGMDR12 (<i>P</i> &lt; 0.001), and different patterns of fat replacement within each of the muscles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We showed a strong correlation of fat fraction on MRI and fat percentage on muscle biopsy for diseased muscles and validated the use of Dixon fat fraction imaging as an outcome measure in LGMDR12. The inhomogeneous fat replacement within thigh muscles on imaging underlines the risk of analysing only samples of muscles instead of the entire muscles, which has important implications for clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 3","pages":"1468-1481"},"PeriodicalIF":8.9,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5944381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}