Jona Van den Broeck, Hubert Raeymaekers, Erik Cattrysse, Savanah Héréus, Aldo Scafoglieri
Background Muscle mass is a critical indicator of health and functionality, yet its accurate measurement remains challenging. Ultrasound offers a promising alternative, providing cost‐effective, non‐invasive assessments of surrogates of muscle mass: muscle thickness and cross‐sectional area (CSA). This study aims to develop and validate ultrasound‐derived equations for estimating whole‐body muscle mass in healthy Caucasian adults using magnetic resonance imaging (MRI) as the reference standard, incorporating CSA measurements to enhance the accuracy and applicability of these equations. Methods We enrolled 211 healthy Caucasian adults (age: 42.0 years [29.0–58.0], 52% female) for whole‐body MRI and ultrasound examinations, assessing eight muscle thicknesses and seven CSAs across the right arm, trunk and leg. The sample was divided into a development group (two‐thirds) and a cross‐validation group (one‐third). Stepwise multiple regression established ultrasound equations in the development group and cross‐validation group. After successful cross‐validation, the full sample was used to create the most accurate and most practical equations. Results The most accurate equation for estimating whole‐body muscle mass included ultrasound muscle thickness measurements of the forearm extensor, rectus abdominis, rectus femoris, biceps femoris and tibialis anterior muscles, CSA measurements of the triceps brachii and tibialis anterior muscles and sex, weight and BMI. This model achieved an adjusted R2 of 0.942 and a standard error of estimate (SEE) of 1.7 kg. A more practical equation, requiring fewer measurements, focused on ultrasound muscle thickness and CSA of select arm, abdominal and leg muscles, combined with sex and height. This simplified model showed an adjusted R2 of 0.927 and an SEE of 2.0 kg, offering a good balance between accuracy and measurement burden. Conclusions The equations developed in this study enable accurate estimation of whole‐body muscle mass in a Caucasian population using ultrasound. A practical, time‐efficient equation with fewer variables is available alongside a more detailed equation that provides higher accuracy. Importantly, models that combine muscle thickness and CSA measurements demonstrated improved prediction accuracy (higher adjusted R2 and lower SEE) compared to those using muscle thickness alone, supporting the inclusion of CSA in future applications.
{"title":"Novel MRI‐Guided Ultrasound Equations for Whole‐Body Muscle Mass in Caucasian Adults","authors":"Jona Van den Broeck, Hubert Raeymaekers, Erik Cattrysse, Savanah Héréus, Aldo Scafoglieri","doi":"10.1002/jcsm.70242","DOIUrl":"https://doi.org/10.1002/jcsm.70242","url":null,"abstract":"Background Muscle mass is a critical indicator of health and functionality, yet its accurate measurement remains challenging. Ultrasound offers a promising alternative, providing cost‐effective, non‐invasive assessments of surrogates of muscle mass: muscle thickness and cross‐sectional area (CSA). This study aims to develop and validate ultrasound‐derived equations for estimating whole‐body muscle mass in healthy Caucasian adults using magnetic resonance imaging (MRI) as the reference standard, incorporating CSA measurements to enhance the accuracy and applicability of these equations. Methods We enrolled 211 healthy Caucasian adults (age: 42.0 years [29.0–58.0], 52% female) for whole‐body MRI and ultrasound examinations, assessing eight muscle thicknesses and seven CSAs across the right arm, trunk and leg. The sample was divided into a development group (two‐thirds) and a cross‐validation group (one‐third). Stepwise multiple regression established ultrasound equations in the development group and cross‐validation group. After successful cross‐validation, the full sample was used to create the most accurate and most practical equations. Results The most accurate equation for estimating whole‐body muscle mass included ultrasound muscle thickness measurements of the forearm extensor, rectus abdominis, rectus femoris, biceps femoris and tibialis anterior muscles, CSA measurements of the triceps brachii and tibialis anterior muscles and sex, weight and BMI. This model achieved an adjusted <jats:italic>R</jats:italic> <jats:sup>2</jats:sup> of 0.942 and a standard error of estimate (SEE) of 1.7 kg. A more practical equation, requiring fewer measurements, focused on ultrasound muscle thickness and CSA of select arm, abdominal and leg muscles, combined with sex and height. This simplified model showed an adjusted <jats:italic>R</jats:italic> <jats:sup>2</jats:sup> of 0.927 and an SEE of 2.0 kg, offering a good balance between accuracy and measurement burden. Conclusions The equations developed in this study enable accurate estimation of whole‐body muscle mass in a Caucasian population using ultrasound. A practical, time‐efficient equation with fewer variables is available alongside a more detailed equation that provides higher accuracy. Importantly, models that combine muscle thickness and CSA measurements demonstrated improved prediction accuracy (higher adjusted <jats:italic>R</jats:italic> <jats:sup>2</jats:sup> and lower SEE) compared to those using muscle thickness alone, supporting the inclusion of CSA in future applications.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"20 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478379","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}
Background Cancer cachexia is a complex syndrome marked by weight loss and muscle wasting, significantly impacting patient quality of life and survival. Mechanistically, it is characterized by suppressed protein synthesis and enhanced muscle catabolism, with the role of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) becoming increasingly evident. This study aimed to explore ER stress–tolerant factors in muscle wasting and evaluate their potential to prevent muscle loss in cancer cachexia. Methods A genome‐wide CRISPR screening was conducted in the context of ER stress–mediated growth inhibition of C2C12 myoblasts. The candidate genes resistant to ER stress were further evaluated in C2C12 myotubes treated with conditioned medium of Lewis lung adenocarcinoma (LLC) cells. Twelve‐week‐old male mice were administered LLC cells and shRNA against Naa35 via adeno‐associated virus. Four weeks later, tibialis anterior (TA) muscles were analysed for muscle mass, grip strength and molecular changes with quantitative polymerase chain reaction, western blotting and histological analysis. Results CRISPR screening identified Naa35, Naa38 and Naa30, all three components of N‐terminal acetyltransferase C, as key molecules for resistance to ER stress. The atrophic muscles of mice bearing LLC demonstrated an elevation of UPR, as well as 1.64‐fold upregulation of Naa35 protein ( <jats:italic>p</jats:italic> = 0.0072). Among the three branches of the UPR, an ATF6 inhibitor, AEBSF, abolished upregulation of Naa35, Naa38 and Naa30, and an ATF6 activator, AA147, induced Naa35 expression in a dose‐dependent manner ( <jats:italic>p</jats:italic> < 0.001). In cells treated with LLC conditioned medium, Naa35 knockdown reduced the amount of cathepsin K (CTSK) protein, which subsequently resulted in the CTSK‐mediated proteolysis of insulin receptor substrate 1. In LLC‐bearing mice, Naa35 knockdown led to a 65.4% reduction in CTSK protein expression ( <jats:italic>p</jats:italic> < 0.001) and preservation of the phosphorylation levels of protein kinase B ( <jats:italic>p</jats:italic> < 0.0324) and anabolic‐related S6 kinase ( <jats:italic>p</jats:italic> < 0.0375). Concurrently, the expression of catabolism‐related genes was repressed (MuRF1, <jats:italic>p</jats:italic> < 0.0015; MAFbx1, <jats:italic>p</jats:italic> < 0.0265). These alterations were associated with the restoration of TA muscle mass (2.52 ± 0.19 vs. 3.72 ± 0.45 mg/g, <jats:italic>p</jats:italic> = 0.0004), fibre area (1741 ± 992 vs. 2099 ± 1264 mm <jats:sup>2</jats:sup> , <jats:italic>p</jats:italic> < 0.0001), grip strength in all four limbs (0.0328 ± 0.0076 vs. 0.0506 ± 0.0130 N/g, <jats:italic>p</jats:italic> = 0.0295) and wire mesh hanging time (496 ± 331 vs. 1038 ± 370 s, <jats:italic>p</jats:italic> = 0.0406). Conclusions Inhibition of N‐terminal acetyltransferase C prevents ER stress–induced muscle wasting via the downregulation of CTSK and subsequent activati
癌症恶病质是一种以体重减轻和肌肉萎缩为特征的复杂综合征，严重影响患者的生活质量和生存。机制上表现为抑制蛋白质合成和增强肌肉分解代谢，内质网（ER）应激和未折叠蛋白反应（UPR）的作用日益明显。本研究旨在探讨内质网应激耐受因子在肌肉萎缩中的作用，并评估其预防癌症恶病质中肌肉损失的潜力。方法在内质网应激介导的C2C12成肌细胞生长抑制的背景下，进行全基因组范围的CRISPR筛选。在Lewis肺腺癌（LLC）细胞条件培养基处理的C2C12肌管中进一步评估耐内质网应激的候选基因。通过腺相关病毒给12周龄雄性小鼠注射LLC细胞和抗Naa35的shRNA。4周后，采用定量聚合酶链反应、western blotting和组织学方法分析胫骨前肌（TA）的肌肉质量、握力和分子变化。结果通过CRISPR筛选，鉴定出N端乙酰转移酶C的3个组分Naa35、Naa38和Naa30是抵抗内质网胁迫的关键分子。患有LLC的小鼠萎缩肌肉显示UPR升高，Naa35蛋白上调1.64倍（p = 0.0072）。在UPR的三个分支中，ATF6抑制剂AEBSF消除了Naa35、Naa38和Naa30的上调，ATF6激活剂AA147以剂量依赖性方式诱导Naa35的表达（p < 0.001）。在LLC条件培养基处理的细胞中，Naa35敲低降低了组织蛋白酶K （CTSK）蛋白的数量，随后导致CTSK介导的胰岛素受体底物蛋白水解1。在LLC - bearing小鼠中，Naa35敲低导致CTSK蛋白表达降低65.4% (p < 0.001)，蛋白激酶B （p < 0.0324）和合成代谢相关的S6激酶（p < 0.0375）的磷酸化水平保持不变。同时，分解代谢相关基因的表达被抑制（MuRF1, p < 0.0015; MAFbx1, p < 0.0265）。这些变化与TA肌肉质量的恢复（2.52±0.19 vs. 3.72±0.45 mg/g, p = 0.0004）、纤维面积（1741±992 vs. 2099±1264 mm 2, p < 0.0001）、四肢握力（0.0328±0.0076 vs. 0.0506±0.0130 N/g, p = 0.0295）和钢丝网悬挂时间（496±331 vs. 1038±370 s, p = 0.0406）有关。结论N端乙酰转移酶C的抑制通过下调CTSK和随后的合成代谢途径的激活来防止内质网应激诱导的肌肉萎缩。这表明N端乙酰转移酶C是对抗癌症恶病质中肌肉萎缩的潜在治疗靶点。
{"title":"Inhibition of N‐Terminal Acetyltransferase C Mitigates Endoplasmic Reticulum Stress–Mediated Muscle Atrophy in Cancer Cachexia","authors":"Yusaku Kaneko, Tomohiro Hino, Shunta Taminishi, Yayoi Matoba, Daisuke Motooka, Atsushi Hoshino, Satoaki Matoba","doi":"10.1002/jcsm.70249","DOIUrl":"https://doi.org/10.1002/jcsm.70249","url":null,"abstract":"Background Cancer cachexia is a complex syndrome marked by weight loss and muscle wasting, significantly impacting patient quality of life and survival. Mechanistically, it is characterized by suppressed protein synthesis and enhanced muscle catabolism, with the role of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) becoming increasingly evident. This study aimed to explore ER stress–tolerant factors in muscle wasting and evaluate their potential to prevent muscle loss in cancer cachexia. Methods A genome‐wide CRISPR screening was conducted in the context of ER stress–mediated growth inhibition of C2C12 myoblasts. The candidate genes resistant to ER stress were further evaluated in C2C12 myotubes treated with conditioned medium of Lewis lung adenocarcinoma (LLC) cells. Twelve‐week‐old male mice were administered LLC cells and shRNA against Naa35 via adeno‐associated virus. Four weeks later, tibialis anterior (TA) muscles were analysed for muscle mass, grip strength and molecular changes with quantitative polymerase chain reaction, western blotting and histological analysis. Results CRISPR screening identified Naa35, Naa38 and Naa30, all three components of N‐terminal acetyltransferase C, as key molecules for resistance to ER stress. The atrophic muscles of mice bearing LLC demonstrated an elevation of UPR, as well as 1.64‐fold upregulation of Naa35 protein ( <jats:italic>p</jats:italic> = 0.0072). Among the three branches of the UPR, an ATF6 inhibitor, AEBSF, abolished upregulation of Naa35, Naa38 and Naa30, and an ATF6 activator, AA147, induced Naa35 expression in a dose‐dependent manner ( <jats:italic>p</jats:italic> < 0.001). In cells treated with LLC conditioned medium, Naa35 knockdown reduced the amount of cathepsin K (CTSK) protein, which subsequently resulted in the CTSK‐mediated proteolysis of insulin receptor substrate 1. In LLC‐bearing mice, Naa35 knockdown led to a 65.4% reduction in CTSK protein expression ( <jats:italic>p</jats:italic> < 0.001) and preservation of the phosphorylation levels of protein kinase B ( <jats:italic>p</jats:italic> < 0.0324) and anabolic‐related S6 kinase ( <jats:italic>p</jats:italic> < 0.0375). Concurrently, the expression of catabolism‐related genes was repressed (MuRF1, <jats:italic>p</jats:italic> < 0.0015; MAFbx1, <jats:italic>p</jats:italic> < 0.0265). These alterations were associated with the restoration of TA muscle mass (2.52 ± 0.19 vs. 3.72 ± 0.45 mg/g, <jats:italic>p</jats:italic> = 0.0004), fibre area (1741 ± 992 vs. 2099 ± 1264 mm <jats:sup>2</jats:sup> , <jats:italic>p</jats:italic> < 0.0001), grip strength in all four limbs (0.0328 ± 0.0076 vs. 0.0506 ± 0.0130 N/g, <jats:italic>p</jats:italic> = 0.0295) and wire mesh hanging time (496 ± 331 vs. 1038 ± 370 s, <jats:italic>p</jats:italic> = 0.0406). Conclusions Inhibition of N‐terminal acetyltransferase C prevents ER stress–induced muscle wasting via the downregulation of CTSK and subsequent activati","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"146 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478380","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}
Claudius S. Mathy, Lena V. Gast, Christian Holtzhausen, Teresa Gerhalter, Christoph Stuprich, Matthias Türk, Rafael Heiss, Benjamin Marty, Frederik B. Laun, Julia V. Wanschitz, Simon Hametner, Arnd Dörfler, Michael Uder, Tobias Bäuerle, Armin M. Nagel, Rolf Schröder
Background Myofibrillar myopathies (MFM) form a large group of clinically and genetically heterogeneous protein aggregate diseases. We investigated whether a novel quantitative MRI protocol can reveal new aspects of structural and biochemical muscle pathology in three classic MFM subtypes. Methods MRI of the lower legs was performed in nine MFM patients with filamin‐C ( <jats:italic>FLNC</jats:italic> ; <jats:italic>n</jats:italic> = 5), desmin ( <jats:italic>DES</jats:italic> , <jats:italic>n</jats:italic> = 2) and LIM domain binding 3 ( <jats:italic>LDB3</jats:italic> ; <jats:italic>n</jats:italic> = 2) gene mutations, one patient with non‐MFM, filamin‐C related distal myopathy (4 males, 6 females, 51.0 ± 7.7 years) and 10 age‐matched healthy control subjects (5 males, 5 females, 50.0 ± 11.0 years). <jats:sup>1</jats:sup> H MRI at 3 T addressed fatty replacement and edema‐like changes as well as quantitative measurements of proton density fat fraction (PDFF) and water T <jats:sub>2</jats:sub> relaxation times. <jats:sup>39</jats:sup> K/ <jats:sup>23</jats:sup> Na MRI at 7 T was employed to determine apparent tissue potassium and tissue sodium concentrations (aTPC/aTSC). Results T <jats:sub>1</jats:sub> ‐weighted and T <jats:sub>2</jats:sub> ‐weighted STIR imaging showed the highest degree of fat replacement in the soleus and gastrocnemius medialis muscle regions and the highest degree of edema‐like changes in the extensor regions in all 10 myopathy patients. The lowest degree of fat replacement and edema‐like changes was present in the gastrocnemius lateralis muscles. Marked fatty replacement of peroneus muscles was also present in DES‐related MFM and <jats:italic>FLNC</jats:italic> ‐related distal myopathy. Muscular PDFF values were significantly increased in all MFM patients ( <jats:italic>p</jats:italic> = 0.003 ‐ < 0.001) with 60 and 35 of 63 muscles analysed showing increased mean PDFF (> 10% and > 50%). When excluding the muscles with PDFF > 50%, the median water T <jats:sub>2</jats:sub> was significantly increased in all muscle regions of MFM patients with the exception of the tibialis anterior and posterior muscles. Fat‐corrected aTSC values in MFM patients were significantly increased compared to healthy controls (55.6 ± 16.3 mM vs. 23.2 ± 5.5 mM, <jats:italic>p</jats:italic> < 0.001) in all muscles but peroneus muscles, whereas fat‐corrected aTPC values were reduced in all muscles except for gastrocnemius lateralis, tibialis posterior and peroneus muscles (75.4 ± 13.3 mM vs. 108.9 ± 9.9 mM, <jats:italic>p</jats:italic> < 0.001). Conclusions Quantitative PDFF measurements and water T <jats:sub>2</jats:sub> mapping serve as valuable tools to objectively quantify fat and edema‐like changes in MFM. Furthermore, changes in potassium/sodium ion balance in the lower leg muscles of MFM patients could serve as new markers to quantify the extent of biochemical changes in individual muscle regions. Further longitudinal evaluati
背景：肌原纤维性肌病（MFM）是一大类临床和遗传异质性蛋白聚集性疾病。我们研究了一种新的定量MRI方案是否可以揭示三种经典MFM亚型的结构和生化肌肉病理的新方面。方法对9例丝素- C （FLNC, n = 5）、desmin （DES, n = 2）和LIM结构域结合3 （LDB3, n = 2）基因突变的MFM患者，1例非MFM，丝素- C相关远端肌病患者（男4例，女6例，51.0±7.7岁）和10例年龄匹配的健康对照（男5例，女5例，50.0±11.0岁）进行下肢MRI检查。3t时1h MRI处理脂肪替代和水肿样变化，以及质子密度脂肪分数（PDFF）和水t2松弛时间的定量测量。7 T时采用39 K/ 23 Na MRI测定组织钾和组织钠表观浓度（aTPC/aTSC）。结果在所有10例肌病患者中，t1加权和t2加权STIR成像显示比目鱼肌和腓肠肌内侧肌区域的脂肪替代程度最高，伸肌区域的水肿样变化程度最高。最低程度的脂肪替代和水肿样改变出现在腓肠肌外侧。在DES相关的MFM和FLNC相关的远端肌病中也存在腓骨肌明显的脂肪替代。所有MFM患者的肌肉PDFF值均显著增加（p = 0.003‐< 0.001），分析的63块肌肉中有60块和35块显示平均PDFF增加（>； 10%和>； 50%）。当排除PDFF >； 50%的肌肉时，除胫骨前后肌外，MFM患者所有肌肉区域的正中水t2均显著升高。与健康对照组相比，MFM患者除腓骨肌外的所有肌肉的脂肪校正aTSC值均显著增加（55.6±16.3 mM vs. 23.2±5.5 mM, p < 0.001），而除腓骨外侧肌、胫后肌和腓骨肌外的所有肌肉的脂肪校正aTPC值均降低（75.4±13.3 mM vs. 108.9±9.9 mM, p < 0.001）。结论定量PDFF测量和水t2制图是客观量化MFM脂肪和水肿样变化的有价值的工具。此外，MFM患者下肢肌肉中钾/钠离子平衡的变化可以作为量化单个肌肉区域生化变化程度的新标志物。需要进一步的纵向评估来验证他们是否对高度脂肪替代之前的变化敏感。
{"title":"Multi‐Parametric MRI Approach at 3 T and 7 T for Assessing Skeletal Muscle Pathology in Myofibrillar Myopathies: A Pilot Study","authors":"Claudius S. Mathy, Lena V. Gast, Christian Holtzhausen, Teresa Gerhalter, Christoph Stuprich, Matthias Türk, Rafael Heiss, Benjamin Marty, Frederik B. Laun, Julia V. Wanschitz, Simon Hametner, Arnd Dörfler, Michael Uder, Tobias Bäuerle, Armin M. Nagel, Rolf Schröder","doi":"10.1002/jcsm.70245","DOIUrl":"https://doi.org/10.1002/jcsm.70245","url":null,"abstract":"Background Myofibrillar myopathies (MFM) form a large group of clinically and genetically heterogeneous protein aggregate diseases. We investigated whether a novel quantitative MRI protocol can reveal new aspects of structural and biochemical muscle pathology in three classic MFM subtypes. Methods MRI of the lower legs was performed in nine MFM patients with filamin‐C ( <jats:italic>FLNC</jats:italic> ; <jats:italic>n</jats:italic> = 5), desmin ( <jats:italic>DES</jats:italic> , <jats:italic>n</jats:italic> = 2) and LIM domain binding 3 ( <jats:italic>LDB3</jats:italic> ; <jats:italic>n</jats:italic> = 2) gene mutations, one patient with non‐MFM, filamin‐C related distal myopathy (4 males, 6 females, 51.0 ± 7.7 years) and 10 age‐matched healthy control subjects (5 males, 5 females, 50.0 ± 11.0 years). <jats:sup>1</jats:sup> H MRI at 3 T addressed fatty replacement and edema‐like changes as well as quantitative measurements of proton density fat fraction (PDFF) and water T <jats:sub>2</jats:sub> relaxation times. <jats:sup>39</jats:sup> K/ <jats:sup>23</jats:sup> Na MRI at 7 T was employed to determine apparent tissue potassium and tissue sodium concentrations (aTPC/aTSC). Results T <jats:sub>1</jats:sub> ‐weighted and T <jats:sub>2</jats:sub> ‐weighted STIR imaging showed the highest degree of fat replacement in the soleus and gastrocnemius medialis muscle regions and the highest degree of edema‐like changes in the extensor regions in all 10 myopathy patients. The lowest degree of fat replacement and edema‐like changes was present in the gastrocnemius lateralis muscles. Marked fatty replacement of peroneus muscles was also present in DES‐related MFM and <jats:italic>FLNC</jats:italic> ‐related distal myopathy. Muscular PDFF values were significantly increased in all MFM patients ( <jats:italic>p</jats:italic> = 0.003 ‐ < 0.001) with 60 and 35 of 63 muscles analysed showing increased mean PDFF (> 10% and > 50%). When excluding the muscles with PDFF > 50%, the median water T <jats:sub>2</jats:sub> was significantly increased in all muscle regions of MFM patients with the exception of the tibialis anterior and posterior muscles. Fat‐corrected aTSC values in MFM patients were significantly increased compared to healthy controls (55.6 ± 16.3 mM vs. 23.2 ± 5.5 mM, <jats:italic>p</jats:italic> < 0.001) in all muscles but peroneus muscles, whereas fat‐corrected aTPC values were reduced in all muscles except for gastrocnemius lateralis, tibialis posterior and peroneus muscles (75.4 ± 13.3 mM vs. 108.9 ± 9.9 mM, <jats:italic>p</jats:italic> < 0.001). Conclusions Quantitative PDFF measurements and water T <jats:sub>2</jats:sub> mapping serve as valuable tools to objectively quantify fat and edema‐like changes in MFM. Furthermore, changes in potassium/sodium ion balance in the lower leg muscles of MFM patients could serve as new markers to quantify the extent of biochemical changes in individual muscle regions. Further longitudinal evaluati","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"8 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478382","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}
Jacinto Muñoz‐Pardeza, José Francisco López‐Gil, Ignacio Hormazábal‐Aguayo, Mikel Izquierdo, Cesar Agostinis‐Sobrinho, Yasmin Ezzatvar, Antonio García‐Hermoso
Background Compared to their healthy peers, children and adolescents with type 1 diabetes are at an increased risk of adverse changes in body composition, including increased fat mass along with reductions in lean and bone mass. Although exercise has shown promise in improving body mass index in this population, the individual effects of resistance training on specific body composition parameters remain understudied. The aim of the study was to evaluate the effects of resistance training supported by the mHealth application Diactive‐1 on body composition in children and adolescents with type 1 diabetes. Methods Sixty‐two participants with type 1 diabetes (aged 8–18 years old; 48% females) participated in a 24‐week randomised controlled trial and were assigned to either the usual care group ( n = 32) or the exercise group ( n = 30). The intervention was delivered via the Diactive‐1 app, which generates progressive overload resistance training programmes tailored to real‐time glycaemia and provides educational support. Body composition was assessed using anthropometry and dual‐energy X‐ray absorptiometry, with fat, lean and bone measurements standardised by age, sex and ethnicity. Linear mixed models were used to evaluate between‐group differences in change over time under both intention‐to‐treat (ITT) and per‐protocol (PP) approaches. Results At 24 weeks, in the ITT analysis, the intervention group showed greater gains in lean mass (mean difference [MD] = 0.88 kg; 95% confidence interval [CI] 0.09 to 1.66; Hedges' g = 0.568) and whole‐body bone mineral content less head (MD = 32.40 g; 95% CI 6.90 to 57.89; g = 0.644) compared with those in the usual care group. No changes were observed in anthropometric measures, fat mass–related regions or standardised variables ( p > 0.05). The risk of probable sarcopenia was lower in the intervention group (relative risk [RR] = 0.17; 95% CI 0.04 to 0.73; Cohen's h = 0.987) than in the usual care group. Findings were directionally consistent in the PP analysis. Conclusions This intervention increased bone‐related outcomes and was associated with modest gains in lean mass and a lower risk of probable sarcopenia in youths with type 1 diabetes. These findings highlight the potential of the Diactive‐1 app as an adjunct tool to support musculoskeletal health in youths with type 1 diabetes. Trial Registration ClinicalTrials.gov identifier: NCT06048757
与健康的同龄人相比，患有1型糖尿病的儿童和青少年在身体组成方面发生不良变化的风险更高，包括脂肪量增加，瘦骨量减少。尽管运动在改善这一人群的身体质量指数方面显示出了希望，但阻力训练对特定身体成分参数的个体影响仍有待研究。该研究的目的是评估由移动健康应用程序Diactive‐1支持的阻力训练对1型糖尿病儿童和青少年身体成分的影响。方法62名1型糖尿病患者（年龄8-18岁，48%为女性）参加了一项为期24周的随机对照试验，并被分为常规护理组（n = 32）和运动组（n = 30）。干预通过Diactive‐1应用程序提供，该应用程序生成针对实时血糖的渐进式过载阻力训练计划，并提供教育支持。使用人体测量学和双能X线吸收测量法评估身体成分，并根据年龄、性别和种族对脂肪、瘦肉和骨骼进行标准化测量。使用线性混合模型来评估在意向治疗（ITT）和每个方案（PP）方法下组间随时间变化的差异。结果在24周时，在ITT分析中，与常规护理组相比，干预组在瘦体重（平均差[MD] = 0.88 kg； 95%可信区间[CI] 0.09至1.66;Hedges' g = 0.568）和全身骨矿物质含量（MD = 32.40 g; 95% CI 6.90至57.89;g = 0.644）方面有较大的增加。在人体测量、脂肪量相关区域或标准化变量中未观察到变化（p > 0.05）。干预组发生肌少症的风险低于常规护理组（相对危险度[RR] = 0.17; 95% CI = 0.04 ~ 0.73; Cohen’s h = 0.987）。结果在PP分析中方向一致。结论：该干预增加了与骨相关的结果，并与1型糖尿病青少年瘦质量的适度增加和可能的肌肉减少症风险降低相关。这些发现强调了Diactive - 1应用程序作为支持1型糖尿病青少年肌肉骨骼健康的辅助工具的潜力。临床试验注册：ClinicalTrials.gov标识符：NCT06048757
{"title":"Effects of Diactive‐1–Supported Progressive Resistance Training on Body Composition in Youth With Type 1 Diabetes","authors":"Jacinto Muñoz‐Pardeza, José Francisco López‐Gil, Ignacio Hormazábal‐Aguayo, Mikel Izquierdo, Cesar Agostinis‐Sobrinho, Yasmin Ezzatvar, Antonio García‐Hermoso","doi":"10.1002/jcsm.70257","DOIUrl":"https://doi.org/10.1002/jcsm.70257","url":null,"abstract":"Background Compared to their healthy peers, children and adolescents with type 1 diabetes are at an increased risk of adverse changes in body composition, including increased fat mass along with reductions in lean and bone mass. Although exercise has shown promise in improving body mass index in this population, the individual effects of resistance training on specific body composition parameters remain understudied. The aim of the study was to evaluate the effects of resistance training supported by the mHealth application Diactive‐1 on body composition in children and adolescents with type 1 diabetes. Methods Sixty‐two participants with type 1 diabetes (aged 8–18 years old; 48% females) participated in a 24‐week randomised controlled trial and were assigned to either the usual care group ( <jats:italic>n</jats:italic> = 32) or the exercise group ( <jats:italic>n</jats:italic> = 30). The intervention was delivered via the Diactive‐1 app, which generates progressive overload resistance training programmes tailored to real‐time glycaemia and provides educational support. Body composition was assessed using anthropometry and dual‐energy X‐ray absorptiometry, with fat, lean and bone measurements standardised by age, sex and ethnicity. Linear mixed models were used to evaluate between‐group differences in change over time under both intention‐to‐treat (ITT) and per‐protocol (PP) approaches. Results At 24 weeks, in the ITT analysis, the intervention group showed greater gains in lean mass (mean difference [MD] = 0.88 kg; 95% confidence interval [CI] 0.09 to 1.66; Hedges' <jats:italic>g</jats:italic> = 0.568) and whole‐body bone mineral content less head (MD = 32.40 g; 95% CI 6.90 to 57.89; <jats:italic>g</jats:italic> = 0.644) compared with those in the usual care group. No changes were observed in anthropometric measures, fat mass–related regions or standardised variables ( <jats:italic>p</jats:italic> > 0.05). The risk of probable sarcopenia was lower in the intervention group (relative risk [RR] = 0.17; 95% CI 0.04 to 0.73; Cohen's <jats:italic>h</jats:italic> = 0.987) than in the usual care group. Findings were directionally consistent in the PP analysis. Conclusions This intervention increased bone‐related outcomes and was associated with modest gains in lean mass and a lower risk of probable sarcopenia in youths with type 1 diabetes. These findings highlight the potential of the Diactive‐1 app as an adjunct tool to support musculoskeletal health in youths with type 1 diabetes. Trial Registration <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"http://ClinicalTrials.gov\">ClinicalTrials.gov</jats:ext-link> identifier: NCT06048757","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"273 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478381","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}
Paige C. Arneson‐Wissink, Katherine Pelz, Beth Worley, Heike Mendez, Peter Pham, Parham Diba, Peter R. Levasseur, Grace McCarthy, Alex Chitsazan, Jonathan R. Brody, Aaron J. Grossberg
Background Cachexia is defined by chronic loss of fat and muscle, is a frequent complication of pancreatic ductal adenocarcinoma (PDAC) and negatively impacts patient outcomes. Nutritional supplementation cannot fully reverse tissue wasting, and the mechanisms underlying this phenotype are unclear. This work aims to define the relative contributions of catabolism and anabolism to adipose wasting in PDAC‐bearing mice. Human antigen R (HuR) is an RNA‐binding protein recently shown to suppress adipogenesis. We hypothesize that fat wasting results from a loss of adipose anabolism driven by increased HuR activity in adipocytes of PDAC‐bearing mice. Methods Adult C57BL/6J mice received orthotopic PDAC cell ( KrasG12D ; p53R172H/+ ; Pdx1‐cre ) (PDAC) or PBS (sham) injections. Mice exhibiting moderate cachexia (9 days after injection) were fasted for 24 h, or fasted 24 h and refed 24 h before euthanasia. A separate cohort of PDAC mice were treated with an established HuR inhibitor (KH‐3, 100 mg/kg) and subjected to the fast/refeed paradigm. We analysed body mass, gross fat pad mass and adipose tissue mRNA expression. We quantified lipolytic rate as the normalized quantity of glycerol released from 3T3‐L1 adipocytes in vitro and gonadal fat pads (gWAT) ex vivo. Results 3T3‐L1 adipocytes treated with PDAC cell conditioned media (CM) had lower expression of lipolysis and lipogenesis genes than control cells and did not display elevated lipolysis as measured by liberated glycerol. PDAC gWAT cultured ex vivo displayed decreased lipolysis compared to sham gWAT (−54.7%). PDAC and sham mice lost equivalent fat mass after a 24 h fast; however, PDAC mice could not restore inguinal fat pads (iWAT) (−40.5%) or gWAT (−31.8%) mass after refeeding. RNAseq revealed 572 differentially expressed genes in gWAT from PDAC compared to sham mice. Downregulated genes ( n = 126) were associated with adipogenesis (adj p = 0.05), and expression of adipogenesis master regulators Pparg and Cebpa were reduced in gWAT from PDAC mice. Immunohistochemistry revealed increased HuR staining in gWAT (+74.9%) and iWAT (+41.2%) from PDAC mice. Inhibiting HuR binding restored lipogenesis in refed animals with a concomitant increase in iWAT mass (+131.7%). Conclusions Our work highlights deficient adipose anabolism as a driver of reduced lipid content in 3T3‐L1 adipocytes treated with PDAC conditioned media and PDAC mice. The small molecule KH‐3, which disrupts HuR binding, restored adipose anabolism in PDAC mice. This highlights HuR as a potentially targetable regulatory node for adipose anabolism in cancer cachexia.
{"title":"Impaired Adipose Anabolism in Pancreatic Cancer Cachexia Is Reversed by HuR Inhibition","authors":"Paige C. Arneson‐Wissink, Katherine Pelz, Beth Worley, Heike Mendez, Peter Pham, Parham Diba, Peter R. Levasseur, Grace McCarthy, Alex Chitsazan, Jonathan R. Brody, Aaron J. Grossberg","doi":"10.1002/jcsm.70253","DOIUrl":"https://doi.org/10.1002/jcsm.70253","url":null,"abstract":"Background Cachexia is defined by chronic loss of fat and muscle, is a frequent complication of pancreatic ductal adenocarcinoma (PDAC) and negatively impacts patient outcomes. Nutritional supplementation cannot fully reverse tissue wasting, and the mechanisms underlying this phenotype are unclear. This work aims to define the relative contributions of catabolism and anabolism to adipose wasting in PDAC‐bearing mice. Human antigen R (HuR) is an RNA‐binding protein recently shown to suppress adipogenesis. We hypothesize that fat wasting results from a loss of adipose anabolism driven by increased HuR activity in adipocytes of PDAC‐bearing mice. Methods Adult C57BL/6J mice received orthotopic PDAC cell ( <jats:italic>Kras</jats:italic> <jats:sup> <jats:italic>G12D</jats:italic> </jats:sup> ; <jats:italic>p53</jats:italic> <jats:sup> <jats:italic>R172H/+</jats:italic> </jats:sup> ; <jats:italic>Pdx1‐cre</jats:italic> ) (PDAC) or PBS (sham) injections. Mice exhibiting moderate cachexia (9 days after injection) were fasted for 24 h, or fasted 24 h and refed 24 h before euthanasia. A separate cohort of PDAC mice were treated with an established HuR inhibitor (KH‐3, 100 mg/kg) and subjected to the fast/refeed paradigm. We analysed body mass, gross fat pad mass and adipose tissue mRNA expression. We quantified lipolytic rate as the normalized quantity of glycerol released from 3T3‐L1 adipocytes in vitro and gonadal fat pads (gWAT) ex vivo. Results 3T3‐L1 adipocytes treated with PDAC cell conditioned media (CM) had lower expression of lipolysis and lipogenesis genes than control cells and did not display elevated lipolysis as measured by liberated glycerol. PDAC gWAT cultured ex vivo displayed decreased lipolysis compared to sham gWAT (−54.7%). PDAC and sham mice lost equivalent fat mass after a 24 h fast; however, PDAC mice could not restore inguinal fat pads (iWAT) (−40.5%) or gWAT (−31.8%) mass after refeeding. RNAseq revealed 572 differentially expressed genes in gWAT from PDAC compared to sham mice. Downregulated genes ( <jats:italic>n</jats:italic> = 126) were associated with adipogenesis (adj <jats:italic>p</jats:italic> = 0.05), and expression of adipogenesis master regulators <jats:italic>Pparg</jats:italic> and <jats:italic>Cebpa</jats:italic> were reduced in gWAT from PDAC mice. Immunohistochemistry revealed increased HuR staining in gWAT (+74.9%) and iWAT (+41.2%) from PDAC mice. Inhibiting HuR binding restored lipogenesis in refed animals with a concomitant increase in iWAT mass (+131.7%). Conclusions Our work highlights deficient adipose anabolism as a driver of reduced lipid content in 3T3‐L1 adipocytes treated with PDAC conditioned media and PDAC mice. The small molecule KH‐3, which disrupts HuR binding, restored adipose anabolism in PDAC mice. This highlights HuR as a potentially targetable regulatory node for adipose anabolism in cancer cachexia.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"96 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478378","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}
Yin Li, Jialing Rao, Weiyan Lai, Yuxiang Sun, Hongchun Lin, Jun Zhang, Zengchun Ye, Zhaoyong Hu, Hui Peng
Objectives High glucose induces mitochondrial dysfunction in podocytes, contributing to the development of diabetic nephropathy (DN). There is increasing evidence that muscles play a protective role by secreting myokines into the kidneys. Here, we investigated how skeletal muscle influences podocyte health via muscle–kidney crosstalk. Methods To increase myokine release, we overexpressed PGC‐1α specifically in skeletal muscle (mPGC‐1α) and crossed these mice with db/m mice to generate diabetic mPGC‐1α:db/db mice. In parallel, db/db mice were treated intraperitoneally with recombinant murine interleukin‐15 (IL‐15). Mechanistic studies were performed using isolated primary podocytes and cultured podocyte cell lines. Results Compared with db/db controls, mPGC‐1α:db/db mice exhibited reduced urinary albumin excretion ( p < 0.001), mesangial matrix expansion ( p < 0.001), glomerular basement membrane thickening ( p < 0.001) and urinary podocin excretion ( p < 0.001), along with increased podocyte number ( p < 0.001). Podocytes from mPGC‐1α:db/db mice showed higher expression of Nephrin and COX IV ( p < 0.05) and upregulation of multiple mitochondrial function‐related genes, notably OPA1 ( p < 0.05). Skeletal muscle from mPGC‐1α:db/db mice displayed elevated IL‐15 mRNA ( p < 0.05) and protein ( p < 0.01) levels, accompanied by increased plasma IL‐15 concentrations ( p < 0.05). IL‐15 treatment enhanced podocyte mitochondrial respiration, including basal oxygen consumption rate (OCR, p < 0.05), ATP‐coupled respiration ( p < 0.05) and maximal respiration ( p < 0.05). IL‐15 preserved mitochondrial fusion under high‐glucose conditions by increasing OPA1 expression ( p < 0.05) and promoted OPA1 transcription via histone H3 acetylation at its promoter ( p < 0.05). Conclusions Skeletal muscle‐derived IL‐15 mediates renal protection by maintaining mitochondrial fusion in podocytes during DN progression. Targeting this pathway may offer a therapeutic strategy to preserve kidney function and slow progression to end‐stage renal disease.
{"title":"IL‐15 Links Muscle–Kidney Crosstalk to Preserving Podocyte Mitochondrial Fusion and Attenuating Diabetic Nephropathy","authors":"Yin Li, Jialing Rao, Weiyan Lai, Yuxiang Sun, Hongchun Lin, Jun Zhang, Zengchun Ye, Zhaoyong Hu, Hui Peng","doi":"10.1002/jcsm.70256","DOIUrl":"https://doi.org/10.1002/jcsm.70256","url":null,"abstract":"Objectives High glucose induces mitochondrial dysfunction in podocytes, contributing to the development of diabetic nephropathy (DN). There is increasing evidence that muscles play a protective role by secreting myokines into the kidneys. Here, we investigated how skeletal muscle influences podocyte health via muscle–kidney crosstalk. Methods To increase myokine release, we overexpressed PGC‐1α specifically in skeletal muscle (mPGC‐1α) and crossed these mice with db/m mice to generate diabetic mPGC‐1α:db/db mice. In parallel, db/db mice were treated intraperitoneally with recombinant murine interleukin‐15 (IL‐15). Mechanistic studies were performed using isolated primary podocytes and cultured podocyte cell lines. Results Compared with db/db controls, mPGC‐1α:db/db mice exhibited reduced urinary albumin excretion ( <jats:italic>p</jats:italic> < 0.001), mesangial matrix expansion ( <jats:italic>p</jats:italic> < 0.001), glomerular basement membrane thickening ( <jats:italic>p</jats:italic> < 0.001) and urinary podocin excretion ( <jats:italic>p</jats:italic> < 0.001), along with increased podocyte number ( <jats:italic>p</jats:italic> < 0.001). Podocytes from mPGC‐1α:db/db mice showed higher expression of Nephrin and COX IV ( <jats:italic>p</jats:italic> < 0.05) and upregulation of multiple mitochondrial function‐related genes, notably OPA1 ( <jats:italic>p</jats:italic> < 0.05). Skeletal muscle from mPGC‐1α:db/db mice displayed elevated IL‐15 mRNA ( <jats:italic>p</jats:italic> < 0.05) and protein ( <jats:italic>p</jats:italic> < 0.01) levels, accompanied by increased plasma IL‐15 concentrations ( <jats:italic>p</jats:italic> < 0.05). IL‐15 treatment enhanced podocyte mitochondrial respiration, including basal oxygen consumption rate (OCR, <jats:italic>p</jats:italic> < 0.05), ATP‐coupled respiration ( <jats:italic>p</jats:italic> < 0.05) and maximal respiration ( <jats:italic>p</jats:italic> < 0.05). IL‐15 preserved mitochondrial fusion under high‐glucose conditions by increasing OPA1 expression ( <jats:italic>p</jats:italic> < 0.05) and promoted OPA1 transcription via histone H3 acetylation at its promoter ( <jats:italic>p</jats:italic> < 0.05). Conclusions Skeletal muscle‐derived IL‐15 mediates renal protection by maintaining mitochondrial fusion in podocytes during DN progression. Targeting this pathway may offer a therapeutic strategy to preserve kidney function and slow progression to end‐stage renal disease.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"114 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471083","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}
Catalina Matias, Paige L. Snider, Elizabeth A. Sierra Potchanant, Joshua R. Huot, Rahul Raghav, Michael T. Chin, Simon J. Conway, Jeffrey J. Brault
Barth syndrome (BTHS) is a rare X-linked mitochondrial disorder caused by mutations in the TAFAZZIN gene, which disrupts cardiolipin (CL) remodelling and mitochondrial function. While cardiac manifestations of BTHS are well characterized in male patients, the mechanisms underlying skeletal muscle weakness and fatigability are poorly understood.
{"title":"Deficient Cardiolipin Remodelling Alters Muscle Fibre Composition and Neuromuscular Connectivity in Barth Syndrome","authors":"Catalina Matias, Paige L. Snider, Elizabeth A. Sierra Potchanant, Joshua R. Huot, Rahul Raghav, Michael T. Chin, Simon J. Conway, Jeffrey J. Brault","doi":"10.1002/jcsm.70246","DOIUrl":"https://doi.org/10.1002/jcsm.70246","url":null,"abstract":"Barth syndrome (BTHS) is a rare X-linked mitochondrial disorder caused by mutations in the <i>TAFAZZIN</i> gene, which disrupts cardiolipin (CL) remodelling and mitochondrial function. While cardiac manifestations of BTHS are well characterized in male patients, the mechanisms underlying skeletal muscle weakness and fatigability are poorly understood.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"87 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465946","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}
F. A. Bogaards, Inge Groenendijk, Thies Gehrmann, Marian Beekman, Nico Lakenberg, H. Eka D. Suchiman, Lisette C. P. G. M. de Groot, Marcel J. T. Reinders, P. Eline Slagboom
Background Nutritional weight‐loss interventions are known to reduce bone mineral density (BMD), which can be prevented by adding (resistance) exercise training. However, this combined effect is not well studied in non‐obese adults. In addition, the association between biomarkers and metabolite‐based composite health markers with changes in BMD in such an intervention has not been studied as thoroughly. Objective The aims of the current study were to investigate the effect of a combined nutritional and activity lifestyle intervention on lumbar spine and total body BMD in healthy middle‐aged to older adults, and to relate these effects to a selection of immune‐metabolic biomarkers, muscle mass and fat mass measurements, and two composite metabolite‐based health scores. Methods In this ancillary study of the single‐arm Growing Old TOgether (GOTO) trial (trial registration number GOTNL3301 [ https://onderzoekmetmensen.nl/nl/trial/27183 ], NL‐ OMON27183 ), 134 participants (mean age 62.9 years, 49% female) undertook a 13‐week lifestyle modification, incorporating 12.5% caloric restriction and 12.5% increase in physical activity. The impact on lumbar spine and total body BMD was evaluated using dual‐energy X‐ray absorptiometry (DEXA). The intervention effect on BMD was related to changes in immune‐metabolic biomarkers and two metabolite‐based immune‐metabolic health scores. Results The trial significantly reduced bodyweight with 3.3 and 3.4 kg, consisting of 1.4 and 1.1 kg lean mass, in males (fdr < 0.001) and females (fdr < 0.001), respectively. Lean mass reduced by 1.4 kg in males (fdr < 0.001) and 1.1 kg in females (fdr < 0.001), whereas total body fat% reduced significantly with −1.5% (fdr < 0.001) in males and −1.5% (fdr < 0.001) in females. In males, lumbar spine BMD increased with 3.0% (fdr < 0.001) and total body BMD with 0.7% (fdr = 0.002). In females, the lumbar spine BMD had a trend in the upwards direction (1.2%, fdr = 0.09) and the total body BMD remained stable (0.4%, fdr = 0.07). In males, the increase in lumbar spine BMD was significantly associated with decreased weight (fdr = 0.001) and with decreased body and trunk fat% (fdr = 0.001, fdr = 0.001) and improved immune‐metabolic health (fdr = 0.02). Males with higher BMD but a poor metabolite‐based health score at baseline had a stronger increase in lumbar spine BMD (fdr = 0.03). Conclusions A combined nutritional and activity lifestyle intervention significantly improved BMD of males with good bone health at baseline while at the same time improving metabolic health. Nutritional weight‐loss interventions may not harm BMD when combined with exercise.
{"title":"Effects of a Combined Dietary and Physical Activity Intervention on Bone Density, Lean Mass and Fat Mass in Adults: The GOTO Trial","authors":"F. A. Bogaards, Inge Groenendijk, Thies Gehrmann, Marian Beekman, Nico Lakenberg, H. Eka D. Suchiman, Lisette C. P. G. M. de Groot, Marcel J. T. Reinders, P. Eline Slagboom","doi":"10.1002/jcsm.70226","DOIUrl":"https://doi.org/10.1002/jcsm.70226","url":null,"abstract":"Background Nutritional weight‐loss interventions are known to reduce bone mineral density (BMD), which can be prevented by adding (resistance) exercise training. However, this combined effect is not well studied in non‐obese adults. In addition, the association between biomarkers and metabolite‐based composite health markers with changes in BMD in such an intervention has not been studied as thoroughly. Objective The aims of the current study were to investigate the effect of a combined nutritional and activity lifestyle intervention on lumbar spine and total body BMD in healthy middle‐aged to older adults, and to relate these effects to a selection of immune‐metabolic biomarkers, muscle mass and fat mass measurements, and two composite metabolite‐based health scores. Methods In this ancillary study of the single‐arm Growing Old TOgether (GOTO) trial (trial registration number GOTNL3301 [ <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"https://onderzoekmetmensen.nl/nl/trial/27183\">https://onderzoekmetmensen.nl/nl/trial/27183</jats:ext-link> ], NL‐ <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON27183\">OMON27183</jats:ext-link> ), 134 participants (mean age 62.9 years, 49% female) undertook a 13‐week lifestyle modification, incorporating 12.5% caloric restriction and 12.5% increase in physical activity. The impact on lumbar spine and total body BMD was evaluated using dual‐energy X‐ray absorptiometry (DEXA). The intervention effect on BMD was related to changes in immune‐metabolic biomarkers and two metabolite‐based immune‐metabolic health scores. Results The trial significantly reduced bodyweight with 3.3 and 3.4 kg, consisting of 1.4 and 1.1 kg lean mass, in males (fdr < 0.001) and females (fdr < 0.001), respectively. Lean mass reduced by 1.4 kg in males (fdr < 0.001) and 1.1 kg in females (fdr < 0.001), whereas total body fat% reduced significantly with −1.5% (fdr < 0.001) in males and −1.5% (fdr < 0.001) in females. In males, lumbar spine BMD increased with 3.0% (fdr < 0.001) and total body BMD with 0.7% (fdr = 0.002). In females, the lumbar spine BMD had a trend in the upwards direction (1.2%, fdr = 0.09) and the total body BMD remained stable (0.4%, fdr = 0.07). In males, the increase in lumbar spine BMD was significantly associated with decreased weight (fdr = 0.001) and with decreased body and trunk fat% (fdr = 0.001, fdr = 0.001) and improved immune‐metabolic health (fdr = 0.02). Males with higher BMD but a poor metabolite‐based health score at baseline had a stronger increase in lumbar spine BMD (fdr = 0.03). Conclusions A combined nutritional and activity lifestyle intervention significantly improved BMD of males with good bone health at baseline while at the same time improving metabolic health. Nutritional weight‐loss interventions may not harm BMD when combined with exercise.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"7 18 1","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373859","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}
I. Baïche, H. Hachicha, T. Ragot, et al., “ Enhanced Expression of IL32 mRNA in Skeletal Muscles in the Context of Head and Neck Carcinomas” Journal of Cachexia, Sarcopenia and Muscle17, no. 1 (2026): e70160, https://doi.org/10.1002/jcsm.70160.
In the list of authors, the name ‘Filippo Dall'Ollio’ was misspelled. It should be corrected to ‘Filippo Dall'Olio’.
We apologize for this error.
I. Baïche， H. Hachicha， T. Ragot等，“头颈癌背景下骨骼肌中IL32 mRNA的表达增强”，《恶病质、肌少症与肌肉杂志》，第17期。1 (2026): e70160, https://doi.org/10.1002/jcsm.70160。在作者名单中，“菲利波·达尔·奥利奥”这个名字拼错了。应该更正为“菲利普·达尔奥利奥”。我们为这个错误道歉。
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{"title":"Menopause and Muscle: Closer to Answers, but Significant Questions Remain.","authors":"Stuart M Phillips","doi":"10.1002/jcsm.70248","DOIUrl":"10.1002/jcsm.70248","url":null,"abstract":"","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"17 2","pages":"e70248"},"PeriodicalIF":9.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147300445","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}
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