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Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake 富含蛋白质的汤和每周锻炼可改善肌肉健康:针对蛋白质摄入不足的中老年人的随机试验
IF 9.4 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-20 DOI: 10.1002/jcsm.13481
Li-Ning Peng, Ming-Hsien Lin, Sung-Hua Tseng, Ko-Han Yen, Huei-Fang Lee, Fei-Yuan Hsiao, Liang-Kung Chen
<div> <section> <h3> Background</h3> <p>Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake.</p> </section> <section> <h3> Methods</h3> <p>An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24–30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition.</p> </section> <section> <h3> Results</h3> <p>In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, <i>P</i> for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, <i>P</i> for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, <i>P</i> for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, <i>P</i> for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, <i>P</i> for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, <i>P</i> for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, <i>P</i> for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 μg/dL, <i>P</i> for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, <i>P</i> for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (β = 0.71, 95% CI: 6.88 to 40.79, <i>P</i> = 0.006), five-time sit-to-stand test (β = −0.87, 95% CI: −1.59 to −0.15, <i>P</i> = 0.017), MNA score (β = 0.96, 95% CI: 0.20 to 1.71, <i>P</i> = 0.013), serum triglycerides (β = −15.01, 95% CI: −27.83 to −2.20, <i>P</i> = 0.022), LDL-C (β = −9.23, 9
背景先前的研究强调了补充蛋白质对成年人运动后肌肉功能的协同影响;然而,对于蛋白质摄入不足的人来说,支持这种综合效应的证据并不充分,也不一致。本研究旨在探讨富含蛋白质的汤与运动相结合对蛋白质摄入量不足的中老年人的肌肉健康和新陈代谢的功效。干预组饮用富含蛋白质的汤(每天 24-30 克蛋白质),每周锻炼 1 小时,对照组则接受健康教育。结果在这项试验中,100 名随机参与者中有 97 人(平均年龄:64.65 ± 4.84 岁,81.8% 为女性)完成了研究(干预组 47 人,对照组 50 人)。与基线结果相比,在干预 1 个月和 3 个月时,腰围(83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 厘米,趋势 P = 0.046)、6 分钟步行距离(525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 米,趋势 P = 0.001)、五次坐立时间(7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s,P=0.001)、握力(26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg,P=0.001)和 MNA 评分(26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72,P=0.001)。干预后,血清甘油三酯明显降低(105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL,趋势 P = 0.023),高密度脂蛋白胆固醇增加(60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL,P=0.02)和 DHEA-S 水平(97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 μg/dL,P=0.002)。两组的血清肌生长激素没有差异,但对照组的血清瘦素水平显著增加(9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL,P=0.016)。干预组在 6 分钟步行距离(β = 0.71,95% CI:6.88 至 40.79,P = 0.006)、五次坐立测试(β = -0.87,95% CI:-1.59 至 -0.15,P = 0.017)方面有更大改善。15,P = 0.017)、MNA 评分(β = 0.96,95% CI:0.20 至 1.71,P = 0.013)、血清甘油三酯(β = -15.01,95% CI:-27.83 至 -2.20,P = 0.022)、低密度脂蛋白胆固醇(β = -9.23,95% CI:-16.98 至 -1.结论富含蛋白质的汤加每周锻炼 12 周可显著改善蛋白质摄入不足的中老年人的体能、血脂状况和 DHEA-S 水平,但需要对干预措施的长期益处进行评估研究。
{"title":"Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake","authors":"Li-Ning Peng,&nbsp;Ming-Hsien Lin,&nbsp;Sung-Hua Tseng,&nbsp;Ko-Han Yen,&nbsp;Huei-Fang Lee,&nbsp;Fei-Yuan Hsiao,&nbsp;Liang-Kung Chen","doi":"10.1002/jcsm.13481","DOIUrl":"10.1002/jcsm.13481","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (&lt;1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24–30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, &lt;i&gt;P&lt;/i&gt; for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, &lt;i&gt;P&lt;/i&gt; for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, &lt;i&gt;P&lt;/i&gt; for trend &lt;0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, &lt;i&gt;P&lt;/i&gt; for trend &lt;0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, &lt;i&gt;P&lt;/i&gt; for trend &lt;0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, &lt;i&gt;P&lt;/i&gt; for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, &lt;i&gt;P&lt;/i&gt; for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 μg/dL, &lt;i&gt;P&lt;/i&gt; for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, &lt;i&gt;P&lt;/i&gt; for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (β = 0.71, 95% CI: 6.88 to 40.79, &lt;i&gt;P&lt;/i&gt; = 0.006), five-time sit-to-stand test (β = −0.87, 95% CI: −1.59 to −0.15, &lt;i&gt;P&lt;/i&gt; = 0.017), MNA score (β = 0.96, 95% CI: 0.20 to 1.71, &lt;i&gt;P&lt;/i&gt; = 0.013), serum triglycerides (β = −15.01, 95% CI: −27.83 to −2.20, &lt;i&gt;P&lt;/i&gt; = 0.022), LDL-C (β = −9.23, 9","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"15 4","pages":"1348-1357"},"PeriodicalIF":9.4,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622771","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}
引用次数: 0
DNA methylation of skeletal muscle function-related secretary factors identifies FGF2 as a potential biomarker for sarcopenia 骨骼肌功能相关秘书因子的 DNA 甲基化确定 FGF2 是肌少症的潜在生物标志物
IF 8.9 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-20 DOI: 10.1002/jcsm.13472
Jia-Wen Li, Zheng-Kai Shen, Yu-Shuang Lin, Zhi-Yue Wang, Mei-Lin Li, Hui-Xian Sun, Quan Wang, Can Zhao, Jin-Shui Xu, Xiang Lu, Wei Gao
<div> <section> <h3> Background</h3> <p>Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia.</p> </section> <section> <h3> Methods</h3> <p>The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation-specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis.</p> </section> <section> <h3> Results</h3> <p>Among 1149 cytosine-phosphate-guanine (CpG) sites of 27 skeletal muscle function-related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation-specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (<i>r</i> = 0.372, <i>P</i> < 0.001), grip strength (<i>r</i> = 0.334, <i>P</i> < 0.001), and gait speed (<i>r</i> = 0.411, <i>P</i> < 0.001). ROC curve analysis indicated that the optimal cut-off value of FGF2_30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC = 0.807, 95% CI = 0.756–0.858, <i>P</i> < 0.001). Multivariate logistic regression analyses showed that lower FGF2_30 methylation level (<0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR = 9.223, 95% CI: 6.614–12.861, <i>P</i> < 0.001).</p> </section> <section>
背景肌肉疏松症的特征是肌肉质量和功能因衰老而逐渐丧失。DNA 甲基化已被确认在骨骼肌功能障碍中扮演重要角色。本研究的目的是探讨肌肉疏松症患者全血样本中骨骼肌功能相关因子的甲基化变化。方法利用 MethlTarget™ DNA 甲基化分析平台,分析 50 名肌肉疏松症老年人(年龄≥65 岁)和 50 名年龄与性别匹配的非肌肉疏松症患者的整体 DNA 甲基化水平。候选差异甲基化区域(DMRs)在另外两个独立的更大集合中通过甲基化特异性 PCR(MSP)得到进一步验证,并通过热测序得到确认。利用接收者操作特征(ROC)曲线分析确定了成纤维细胞生长因子 2 (FGF2)_30 甲基化的最佳临界水平,并测量了 ROC 曲线下的面积(AUC)。结果在27个骨骼肌功能相关秘书因子的1149个胞嘧啶-磷酸鸟嘌呤(CpG)位点中,发现了17个不同甲基化CpG位点和7个不同甲基化区域(DMRs)。进一步的甲基化特异性聚合酶链反应发现,成纤维细胞生长因子 2 (FGF2)_30 的甲基化水平在肌肉疏松症患者中较低,而且随着肌肉疏松症严重程度的增加,甲基化水平也随之降低。相关分析表明,FGF2_30的甲基化水平与ASMI(r = 0.372,P < 0.001)、握力(r = 0.334,P < 0.001)和步速(r = 0.411,P < 0.001)呈正相关。ROC 曲线分析表明,预测肌少症的 FGF2_30 甲基化水平的最佳临界值为 0.15,灵敏度为 84.6%,特异度为 70.1%(AUC = 0.807,95% CI = 0.756-0.858, P <0.001)。多变量逻辑回归分析表明,即使在调整了包括年龄、性别和体重指数在内的潜在混杂因素后,较低的 FGF2_30 甲基化水平(<0.15)仍与肌肉疏松症风险的增加显著相关(调整后 OR = 9.223,95% CI: 6.结论我们的研究结果表明,较低的 FGF2_30 甲基化水平与老年人患肌少症的风险和严重程度相关,这表明 FGF2 甲基化水平可作为筛查和评估肌少症的替代生物标志物。
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引用次数: 0
Cross-sectional interactive associations of physical activity and sedentary behaviour with physical capacity across adulthood 体育活动和久坐行为与整个成年期体能的横截面互动关系
IF 8.9 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-18 DOI: 10.1002/jcsm.13457
Jérémy Raffin, Yves Rolland, Mylène Aubertin-Leheudre, Jaqueline Aragoni da Silva, Sophie Guyonnet, Fabien Pillard, Bruno Vellas, Philipe de Souto Barreto, for the INSPIRE group
<div> <section> <h3> Background</h3> <p>The way physical activity (PA) and sedentary behaviour (SB) independently and interactively modify the age-related decline in physical capacity remains poorly understood. This cross-sectional study investigated the independent and interactive associations of PA and SB with physical function and performance throughout the adult life course.</p> </section> <section> <h3> Methods</h3> <p>Data from 499 community-dwelling adults (63% female) aged 20–92 years, involved in the INSPIRE Human Translational Cohort, were used in this cross-sectional study. Daily time spent on moderate-to-vigorous PA (MVPA, min/day) and SB (h/day) was measured with activPAL triaxial accelerometers. Physical function and performance were assessed through the measurement of the 4-m usual gait speed (m/s), handgrip strength (kg), lower-limb strength (isokinetic knee extension torque, N·m), estimated lower-limb power (five-time chair-rise test performance, s) and cardiorespiratory fitness (V̇O<sub>2</sub>max, mL/kg/min). Confounder-adjusted multiple linear and curvilinear regressions were performed to investigate how MVPA, SB and their interactions were associated with the physical outcomes (all square root-transformed except gait speed) throughout the adulthood spectrum.</p> </section> <section> <h3> Results</h3> <p>Interaction analyses revealed that the combination of higher levels of MVPA with lower levels of SB favourably reshaped the negative relationship between handgrip strength and age (age<sup>2</sup> × SB × MVPA: <i>B</i> = −7E-08, SE = 3E-08, <i>P</i> < 0.05). In addition, higher levels of MVPA were independently associated with an improved age-related profile in gait speed (age<sup>2</sup> × MVPA: <i>B</i> = 3E-06, SE = 1E-06, <i>P</i> < 0.05), chair-rise performance (age × MVPA: <i>B</i> = −9E-05, SE = 4E-05, <i>P</i> < 0.05) and V̇O<sub>2</sub>max (MVPA at 21 years: <i>B</i> = 3E-02, SE = 7E-03, <i>P</i> < 0.05; age × MVPA: <i>B</i> = −5E-04, SE = 2E-04, <i>P</i> < 0.05). Conversely, the detrimental association of age with lower-limb muscle strength (age × SB: <i>B</i> = −1E-04, SE = 6E-05, <i>P</i> < 0.05) and chair-rise performance (age × SB: <i>B</i> = 1E-05, SE = 7E-06, <i>P</i> < 0.05) was exacerbated with increasing duration of SB, independently of MVPA. Supplementary analyses further revealed that some of these associations were age and sex specific.</p> </section> <section> <h3> Conclusions</h3> <p>This cross-sectional study demonstrated that reduced sedentary time and increased activity duration we
人们对体力活动(PA)和久坐行为(SB)如何独立并相互作用地改变与年龄相关的体能下降仍然知之甚少。这项横断面研究调查了体力活动和久坐行为在整个成人生命过程中与身体功能和表现之间的独立和交互关系。
{"title":"Cross-sectional interactive associations of physical activity and sedentary behaviour with physical capacity across adulthood","authors":"Jérémy Raffin,&nbsp;Yves Rolland,&nbsp;Mylène Aubertin-Leheudre,&nbsp;Jaqueline Aragoni da Silva,&nbsp;Sophie Guyonnet,&nbsp;Fabien Pillard,&nbsp;Bruno Vellas,&nbsp;Philipe de Souto Barreto,&nbsp;for the INSPIRE group","doi":"10.1002/jcsm.13457","DOIUrl":"10.1002/jcsm.13457","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The way physical activity (PA) and sedentary behaviour (SB) independently and interactively modify the age-related decline in physical capacity remains poorly understood. This cross-sectional study investigated the independent and interactive associations of PA and SB with physical function and performance throughout the adult life course.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Data from 499 community-dwelling adults (63% female) aged 20–92 years, involved in the INSPIRE Human Translational Cohort, were used in this cross-sectional study. Daily time spent on moderate-to-vigorous PA (MVPA, min/day) and SB (h/day) was measured with activPAL triaxial accelerometers. Physical function and performance were assessed through the measurement of the 4-m usual gait speed (m/s), handgrip strength (kg), lower-limb strength (isokinetic knee extension torque, N·m), estimated lower-limb power (five-time chair-rise test performance, s) and cardiorespiratory fitness (V̇O&lt;sub&gt;2&lt;/sub&gt;max, mL/kg/min). Confounder-adjusted multiple linear and curvilinear regressions were performed to investigate how MVPA, SB and their interactions were associated with the physical outcomes (all square root-transformed except gait speed) throughout the adulthood spectrum.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Interaction analyses revealed that the combination of higher levels of MVPA with lower levels of SB favourably reshaped the negative relationship between handgrip strength and age (age&lt;sup&gt;2&lt;/sup&gt; × SB × MVPA: &lt;i&gt;B&lt;/i&gt; = −7E-08, SE = 3E-08, &lt;i&gt;P&lt;/i&gt; &lt; 0.05). In addition, higher levels of MVPA were independently associated with an improved age-related profile in gait speed (age&lt;sup&gt;2&lt;/sup&gt; × MVPA: &lt;i&gt;B&lt;/i&gt; = 3E-06, SE = 1E-06, &lt;i&gt;P&lt;/i&gt; &lt; 0.05), chair-rise performance (age × MVPA: &lt;i&gt;B&lt;/i&gt; = −9E-05, SE = 4E-05, &lt;i&gt;P&lt;/i&gt; &lt; 0.05) and V̇O&lt;sub&gt;2&lt;/sub&gt;max (MVPA at 21 years: &lt;i&gt;B&lt;/i&gt; = 3E-02, SE = 7E-03, &lt;i&gt;P&lt;/i&gt; &lt; 0.05; age × MVPA: &lt;i&gt;B&lt;/i&gt; = −5E-04, SE = 2E-04, &lt;i&gt;P&lt;/i&gt; &lt; 0.05). Conversely, the detrimental association of age with lower-limb muscle strength (age × SB: &lt;i&gt;B&lt;/i&gt; = −1E-04, SE = 6E-05, &lt;i&gt;P&lt;/i&gt; &lt; 0.05) and chair-rise performance (age × SB: &lt;i&gt;B&lt;/i&gt; = 1E-05, SE = 7E-06, &lt;i&gt;P&lt;/i&gt; &lt; 0.05) was exacerbated with increasing duration of SB, independently of MVPA. Supplementary analyses further revealed that some of these associations were age and sex specific.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This cross-sectional study demonstrated that reduced sedentary time and increased activity duration we","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"15 3","pages":"1134-1145"},"PeriodicalIF":8.9,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651412","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}
引用次数: 0
Hepatic signal transducer and activator of transcription-3 signalling drives early-stage pancreatic cancer cachexia via suppressed ketogenesis 肝脏信号转导和转录激活因子-3 信号通过抑制酮体生成驱动早期胰腺癌恶病质的发生
IF 8.9 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-17 DOI: 10.1002/jcsm.13466
Paige C. Arneson-Wissink, Heike Mendez, Katherine Pelz, Jessica Dickie, Alexandra Q. Bartlett, Beth L. Worley, Stephanie M. Krasnow, Robert Eil, Aaron J. Grossberg
<div> <section> <h3> Background</h3> <p>Patients with pancreatic ductal adenocarcinoma (PDAC) often suffer from cachexia, a wasting syndrome that significantly reduces both quality of life and survival. Although advanced cachexia is associated with inflammatory signalling and elevated muscle catabolism, the early events driving wasting are poorly defined. During periods of nutritional scarcity, the body relies on hepatic ketogenesis to generate ketone bodies, and lipid metabolism via ketogenesis is thought to protect muscle from catabolizing during nutritional scarcity.</p> </section> <section> <h3> Methods</h3> <p>We developed an orthotopic mouse model of early PDAC cachexia in 12-week-old C57BL/6J mice. Murine pancreatic cancer cells (KPC) were orthotopically implanted into the pancreas of wild-type, IL-6<sup>−/−</sup>, and hepatocyte STAT3<sup>−/−</sup> male and female mice. Mice were subject to fasting, 50% food restriction, ad libitum feeding or ketogenic diet interventions. We measured longitudinal body composition by EchoMRI, body mass and food intake. At the endpoint, we measured tissue mass, tissue gene expression by quantitative real-time polymerase chain reaction, whole-body calorimetry, circulating hormone levels, faecal protein and lipid content, hepatic lipid content and ketogenic response to medium-chain fatty acid bolus. We assessed muscle atrophy in vivo and C2C12 myotube atrophy in vitro.</p> </section> <section> <h3> Results</h3> <p>Pre-cachectic PDAC mice did not preserve gastrocnemius muscle mass during 3-day food restriction (−13.1 ± 7.7% relative to food-restricted sham, <i>P</i> = 0.0117) and displayed impaired fatty acid oxidation during fasting, resulting in a hypoketotic state (ketogenic response to octanoate bolus, −83.0 ± 17.3%, <i>P</i> = 0.0328; <i>Hmgcs2</i> expression, −28.3 ± 7.6%, <i>P</i> = 0.0004). PDAC human patients display impaired fasting ketones (−46.9 ± 7.1%, <i>P</i> < 0.0001) and elevated circulating interleukin-6 (IL-6) (12.4 ± 16.5-fold increase, <i>P</i> = 0.0001). IL-6<sup>−/−</sup> PDAC mice had improved muscle mass (+35.0 ± 3.9%, <i>P</i> = 0.0031) and ketogenic response (+129.4 ± 44.4%, <i>P</i> = 0.0033) relative to wild-type PDAC mice. Hepatocyte-specific signal transducer and activator of transcription 3 (STAT3) deletion prevented muscle loss (+9.3 ± 4.0%, <i>P</i> = 0.009) and improved fasting ketone levels (+52.0 ± 43.3%, <i>P</i> = 0.018) in PDAC mice. Without affecting tumour growth, a carbohydrate-free diet improved tibialis anterior myofibre diameter (+16.5 ± 3.5%, <i>P</i> = 0.0089), circulating ketone bodies (+333.0 ± 117.6%, <i>P</i> < 0.0001) and <i>Hmgcs2</i> expression (+106.5
背景胰腺导管腺癌(PDAC)患者经常会出现恶病质,这是一种消瘦综合征,会大大降低患者的生活质量和存活率。虽然晚期恶病质与炎症信号传导和肌肉分解代谢增加有关,但导致消瘦的早期事件还不十分明确。在营养匮乏期间,机体依靠肝脏生酮来生成酮体,而通过生酮进行的脂质代谢被认为能保护肌肉在营养匮乏期间不被分解。将小鼠胰腺癌细胞(KPC)正位植入野生型、IL-6-/-和肝细胞STAT3-/-雄性和雌性小鼠的胰腺中。对小鼠进行禁食、50%食物限制、自由采食或生酮饮食干预。我们通过 EchoMRI 测量纵向身体成分、体重和食物摄入量。在终点,我们测量了组织质量、通过实时聚合酶链式反应定量的组织基因表达、全身热量计、循环激素水平、粪便蛋白质和脂质含量、肝脏脂质含量以及对中链脂肪酸栓剂的生酮反应。我们对体内肌肉萎缩和体外 C2C12 肌管萎缩进行了评估。0117),并在禁食期间表现出脂肪酸氧化受损,导致低酮症状态(对辛酸栓的生酮反应,-83.0 ± 17.3%,P = 0.0328;Hmgcs2 表达,-28.3 ± 7.6%,P = 0.0004)。PDAC 人类患者显示出空腹酮体受损(-46.9 ± 7.1%,P = 0.0001)和循环白细胞介素-6(IL-6)升高(12.4 ± 16.5 倍,P = 0.0001)。与野生型 PDAC 小鼠相比,IL-6-/- PDAC 小鼠的肌肉质量(+35.0 ± 3.9%,P = 0.0031)和生酮反应(+129.4 ± 44.4%,P = 0.0033)均有所改善。肝细胞特异性信号转导和激活转录 3 (STAT3) 基因缺失可防止 PDAC 小鼠的肌肉损失(+9.3 ± 4.0%,P = 0.009),并改善空腹酮体水平(+52.0 ± 43.3%,P = 0.018)。在不影响肿瘤生长的情况下,无碳水化合物饮食可改善 PDAC 小鼠的胫骨前肌纤维直径(+16.5 ± 3.5%,P = 0.0089)、循环酮体(+333.0 ± 117.6%,P < 0.0001)和 Hmgcs2 表达(+106.5 ± 36.1%,P < 0.0001)。结论在早期 PDAC 恶病质中,肌肉易消瘦取决于肝脏中炎症驱动的代谢重编程。PDAC 会抑制肝脏中的脂质 β 氧化并损害酮体生成,而在缺乏 IL-6/STAT3 信号的转基因小鼠模型中或通过补充生酮饮食可逆转这种情况。这项研究建立了骨骼肌稳态与肝脏代谢之间的直接联系。对胰腺癌前期患者来说,恢复生酮的饮食和抗炎干预可能是一种可行的预防方法。
{"title":"Hepatic signal transducer and activator of transcription-3 signalling drives early-stage pancreatic cancer cachexia via suppressed ketogenesis","authors":"Paige C. Arneson-Wissink,&nbsp;Heike Mendez,&nbsp;Katherine Pelz,&nbsp;Jessica Dickie,&nbsp;Alexandra Q. Bartlett,&nbsp;Beth L. Worley,&nbsp;Stephanie M. Krasnow,&nbsp;Robert Eil,&nbsp;Aaron J. Grossberg","doi":"10.1002/jcsm.13466","DOIUrl":"10.1002/jcsm.13466","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Patients with pancreatic ductal adenocarcinoma (PDAC) often suffer from cachexia, a wasting syndrome that significantly reduces both quality of life and survival. Although advanced cachexia is associated with inflammatory signalling and elevated muscle catabolism, the early events driving wasting are poorly defined. During periods of nutritional scarcity, the body relies on hepatic ketogenesis to generate ketone bodies, and lipid metabolism via ketogenesis is thought to protect muscle from catabolizing during nutritional scarcity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We developed an orthotopic mouse model of early PDAC cachexia in 12-week-old C57BL/6J mice. Murine pancreatic cancer cells (KPC) were orthotopically implanted into the pancreas of wild-type, IL-6&lt;sup&gt;−/−&lt;/sup&gt;, and hepatocyte STAT3&lt;sup&gt;−/−&lt;/sup&gt; male and female mice. Mice were subject to fasting, 50% food restriction, ad libitum feeding or ketogenic diet interventions. We measured longitudinal body composition by EchoMRI, body mass and food intake. At the endpoint, we measured tissue mass, tissue gene expression by quantitative real-time polymerase chain reaction, whole-body calorimetry, circulating hormone levels, faecal protein and lipid content, hepatic lipid content and ketogenic response to medium-chain fatty acid bolus. We assessed muscle atrophy in vivo and C2C12 myotube atrophy in vitro.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pre-cachectic PDAC mice did not preserve gastrocnemius muscle mass during 3-day food restriction (−13.1 ± 7.7% relative to food-restricted sham, &lt;i&gt;P&lt;/i&gt; = 0.0117) and displayed impaired fatty acid oxidation during fasting, resulting in a hypoketotic state (ketogenic response to octanoate bolus, −83.0 ± 17.3%, &lt;i&gt;P&lt;/i&gt; = 0.0328; &lt;i&gt;Hmgcs2&lt;/i&gt; expression, −28.3 ± 7.6%, &lt;i&gt;P&lt;/i&gt; = 0.0004). PDAC human patients display impaired fasting ketones (−46.9 ± 7.1%, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001) and elevated circulating interleukin-6 (IL-6) (12.4 ± 16.5-fold increase, &lt;i&gt;P&lt;/i&gt; = 0.0001). IL-6&lt;sup&gt;−/−&lt;/sup&gt; PDAC mice had improved muscle mass (+35.0 ± 3.9%, &lt;i&gt;P&lt;/i&gt; = 0.0031) and ketogenic response (+129.4 ± 44.4%, &lt;i&gt;P&lt;/i&gt; = 0.0033) relative to wild-type PDAC mice. Hepatocyte-specific signal transducer and activator of transcription 3 (STAT3) deletion prevented muscle loss (+9.3 ± 4.0%, &lt;i&gt;P&lt;/i&gt; = 0.009) and improved fasting ketone levels (+52.0 ± 43.3%, &lt;i&gt;P&lt;/i&gt; = 0.018) in PDAC mice. Without affecting tumour growth, a carbohydrate-free diet improved tibialis anterior myofibre diameter (+16.5 ± 3.5%, &lt;i&gt;P&lt;/i&gt; = 0.0089), circulating ketone bodies (+333.0 ± 117.6%, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001) and &lt;i&gt;Hmgcs2&lt;/i&gt; expression (+106.5","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"15 3","pages":"975-988"},"PeriodicalIF":8.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620229","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}
引用次数: 0
Lean body mass and the cardiorespiratory phenotype: An ethnic-specific relationship in Hans Chinese women and men 瘦体重与心肺表型:汉族中国女性和男性的种族特异性关系
IF 8.9 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-17 DOI: 10.1002/jcsm.13464
Meihan Guo, Candela Diaz-Canestro, Nicola Riccardo Pugliese, Francesco Paneni, David Montero

Background

Lean body mass (LBM) and the functional capacity of cardiovascular (CV) and respiratory systems constitute a female-specific relationship in European–American individuals. Whether this recent finding be extrapolated to the world's largest ethnic group, that is, Hans Chinese (HC, a population characterized by low LBM), is unknown.

Methods

Healthy HC adults (n = 144, 50% ♀) closely matched by sex, age and physical activity were included. Total and regional (leg, arm and trunk) LBM and body composition were measured via dual-energy X-ray absorptiometry. Cardiac structure, stiffness, central/peripheral haemodynamics and peak O2 consumption (VO2peak) were assessed via transthoracic echocardiography and pulmonary gas analyses at rest and during exercise up to peak effort. Regression analyses determined the sex-specific relationship of LBM with cardiac and aerobic phenotypes.

Results

Total and regional LBM were lower and body fat percentage higher in women compared with men (P < 0.001). In both sexes, total LBM positively associated with left ventricular (LV) mass and peak volumes (r ≥ 0.33, P ≤ 0.005) and negatively with LV end-systolic and central arterial stiffness (r ≥ −0.34, P ≤ 0.004). Total LBM strongly associated with VO2peak (r ≥ 0.60, P < 0.001) and peak cardiac output (r ≥ 0.40, P < 0.001) in women and men. Among regional LBM, leg LBM prominently associated with the arterio-venous O2 difference at peak exercise in both sexes (r ≥ 0.43, P < 0.001). Adjustment by adiposity or CV risk factors did not modify the results.

Conclusions

LBM independently determines internal cardiac dimensions, ventricular mass, distensibility and the capacity to deliver and consume O2 in HC adults irrespective of sex.

背景瘦体重(LBM)与心血管(CV)和呼吸系统的功能能力在欧美人中构成一种女性特有的关系。这一最新发现是否可以推广到世界上最大的人种,即汉族,尚不得而知。方法纳入了性别、年龄和体力活动密切匹配的健康汉族成年人(n = 144,50% ♀)。通过双能 X 射线吸收测量法测量总的和区域(腿部、手臂和躯干)的 LBM 以及身体成分。通过经胸超声心动图和肺气体分析,评估了静息时和运动至峰值时的心脏结构、硬度、中枢/外周血流动力学和峰值氧气消耗量(VO2peak)。回归分析确定了 LBM 与心脏和有氧表型的性别特异性关系。在两性中,总 LBM 与左心室(LV)质量和峰值容量呈正相关(r ≥ 0.33,P ≤ 0.005),与左心室收缩末期和中央动脉僵硬度呈负相关(r ≥ -0.34,P ≤ 0.004)。在女性和男性中,总 LBM 与 VO2 峰值(r ≥ 0.60,P < 0.001)和峰值心输出量(r ≥ 0.40,P < 0.001)密切相关。在区域 LBM 中,腿部 LBM 与男女运动峰值时动静脉 O2 差异显著相关(r ≥ 0.43,P < 0.001)。结论LBM可独立决定HC成人的心脏内部尺寸、心室质量、扩张性以及输送和消耗氧气的能力,与性别无关。
{"title":"Lean body mass and the cardiorespiratory phenotype: An ethnic-specific relationship in Hans Chinese women and men","authors":"Meihan Guo,&nbsp;Candela Diaz-Canestro,&nbsp;Nicola Riccardo Pugliese,&nbsp;Francesco Paneni,&nbsp;David Montero","doi":"10.1002/jcsm.13464","DOIUrl":"10.1002/jcsm.13464","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lean body mass (LBM) and the functional capacity of cardiovascular (CV) and respiratory systems constitute a female-specific relationship in European–American individuals. Whether this recent finding be extrapolated to the world's largest ethnic group, that is, Hans Chinese (HC, a population characterized by low LBM), is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Healthy HC adults (<i>n</i> = 144, 50% ♀) closely matched by sex, age and physical activity were included. Total and regional (leg, arm and trunk) LBM and body composition were measured via dual-energy X-ray absorptiometry. Cardiac structure, stiffness, central/peripheral haemodynamics and peak O<sub>2</sub> consumption (VO<sub>2peak</sub>) were assessed via transthoracic echocardiography and pulmonary gas analyses at rest and during exercise up to peak effort. Regression analyses determined the sex-specific relationship of LBM with cardiac and aerobic phenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Total and regional LBM were lower and body fat percentage higher in women compared with men (<i>P</i> &lt; 0.001). In both sexes, total LBM positively associated with left ventricular (LV) mass and peak volumes (<i>r</i> ≥ 0.33, <i>P</i> ≤ 0.005) and negatively with LV end-systolic and central arterial stiffness (<i>r</i> ≥ −0.34, <i>P</i> ≤ 0.004). Total LBM strongly associated with VO<sub>2peak</sub> (<i>r</i> ≥ 0.60, <i>P</i> &lt; 0.001) and peak cardiac output (<i>r</i> ≥ 0.40, <i>P</i> &lt; 0.001) in women and men. Among regional LBM, leg LBM prominently associated with the arterio-venous O<sub>2</sub> difference at peak exercise in both sexes (<i>r</i> ≥ 0.43, <i>P</i> &lt; 0.001). Adjustment by adiposity or CV risk factors did not modify the results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LBM independently determines internal cardiac dimensions, ventricular mass, distensibility and the capacity to deliver and consume O<sub>2</sub> in HC adults irrespective of sex.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"15 3","pages":"963-974"},"PeriodicalIF":8.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620224","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}
引用次数: 0
Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association 脂联素-瘦素比值与慢性肾脏病发病率:与性别和身体成分有关
IF 9.4 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-17 DOI: 10.1002/jcsm.13475
Hye-Sun Park, Sang Ho Park, Yeseul Seong, Hyo Jeong Kim, Hoon Young Choi, Yumie Rhee, Hyeong Cheon Park, Jong Hyun Jhee

Background

The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition.

Methods

In this prospective community-based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60 mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia.

Results

The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8–3.2] and 0.5 [0.3–0.9] μg/ng, P < 0.001). During a median follow-up of 9.8 [9.5–10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33–0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80–0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI < 23.0 kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m2 and those without sarcopenia.

Conclusions

A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI < 23.0 kg/m2 and sarcopenia.

背景人们对脂肪连接蛋白与瘦素的比率(A/L 比率)与慢性肾脏病(CKD)发病风险之间的关系知之甚少。本研究旨在调查 A/L 比值与慢性肾脏病发病风险之间的关系,并研究这种关系是否因性别和身体成分而异。方法在这个基于社区的前瞻性队列中,对肾功能正常的参与者(N = 5192)进行了分析。基线时的 A/L 比值与发生 CKD 的风险之间的关系采用多变量 Cox 比例危险度分析进行了评估,CKD 的定义是在随访期间有两次或两次以上估计肾小球滤过率为 <60 mL/min/m2 或用量度尺检测蛋白尿≥1+。根据性别、体重指数(BMI)和是否存在肌肉疏松症进行了分组分析。结果参与者的平均年龄为 57.2 ± 8.3 岁,53.2% 为女性。男性的 A/L 比率高于女性(1.5 [0.8-3.2] 和 0.5 [0.3-0.9] μg/ng,P < 0.001)。在中位随访 9.8 [9.5-10.0] 年期间,共发生了 417 例慢性肾功能衰竭事件(每 1000 人年 8.7 例)。与最低四分位数的男性相比,A/L 比值最高四分位数的男性发生 CKD 的风险较低(调整后危险比 [aHR],0.57;95% 置信区间 [CI],0.33-0.99)。此外,A/L 比值每增加 1.0,男性发生 CKD 的风险就会降低 12%(aHR,0.88;95% 置信区间 [CI],0.80-0.97)。然而,在女性中没有观察到明显的相关性。在按体重指数和是否存在肌肉疏松症进行的亚组分析中,体重指数为 23.0 kg/m2 的男性和存在肌肉疏松症的男性中,A/L 比值高与发生慢性肾脏病的风险降低之间的关系是一致的。结论 A/L比值高是男性发生慢性肾脏病风险降低的一个独立标志,尤其是在体重指数(BMI)≥23.0 kg/m2和患有肌肉疏松症的男性中。
{"title":"Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association","authors":"Hye-Sun Park,&nbsp;Sang Ho Park,&nbsp;Yeseul Seong,&nbsp;Hyo Jeong Kim,&nbsp;Hoon Young Choi,&nbsp;Yumie Rhee,&nbsp;Hyeong Cheon Park,&nbsp;Jong Hyun Jhee","doi":"10.1002/jcsm.13475","DOIUrl":"10.1002/jcsm.13475","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective community-based cohort, participants with normal kidney function were analysed (<i>N</i> = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of &lt;60 mL/min/m<sup>2</sup> or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8–3.2] and 0.5 [0.3–0.9] μg/ng, <i>P</i> &lt; 0.001). During a median follow-up of 9.8 [9.5–10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33–0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80–0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI &lt; 23.0 kg/m<sup>2</sup> and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m<sup>2</sup> and those without sarcopenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI &lt; 23.0 kg/m<sup>2</sup> and sarcopenia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"15 4","pages":"1298-1308"},"PeriodicalIF":9.4,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140620081","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}
引用次数: 0
Prognostic impact of muscle mass loss in elderly patients with oesophageal cancer receiving neoadjuvant chemoradiation therapy 接受新辅助化疗的老年食道癌患者肌肉质量下降对预后的影响
IF 8.9 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-13 DOI: 10.1002/jcsm.13462
Jeong Yun Jang, Dongryul Oh, Jae Myoung Noh, Jong-Mu Sun, Hong Kwan Kim, Young Mog Shim
<div> <section> <h3> Background</h3> <p>We aimed to identify the impact of muscle mass on locally advanced oesophageal cancer (LAEC) in elderly patients receiving neoadjuvant chemoradiation therapy (NACRT).</p> </section> <section> <h3> Methods</h3> <p>We reviewed the medical records of 345 patients diagnosed with LAEC who underwent NACRT and surgery. Physical variables, including height, weight, skeletal muscle mass, and laboratory values, were obtained before and after NACRT. Body mass index (BMI, kg/m<sup>2</sup>), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated as height/(weight)<sup>2</sup>, ANC/ALC, platelet count/ALC, and (10 × albumin + 0.05 × ALC), respectively. The cutoff for low muscle mass was 43.0 cm<sup>2</sup>/m<sup>2</sup> for BMI below 25 kg/m<sup>2</sup> and 53.0 cm<sup>2</sup>/m<sup>2</sup> for BMI 25 kg/m<sup>2</sup> or higher. The skeletal muscle index (SMI) was defined as skeletal muscle area/(height)<sup>2</sup> (cm<sup>2</sup>/m<sup>2</sup>). The ΔSMI (%/50 days) was defined as (SMI after NACRT − SMI before NACRT)/interval (days) × 50 (days) to compare changes over the same period. The excessive muscle loss (EML) group was defined as patients with ΔSMI ≤−10% following NACRT. An elderly patient was defined as aged ≥65 years. The primary outcome measure was overall survival (OS).</p> </section> <section> <h3> Results</h3> <p>During a median follow-up of 32.8 months (range, 2.0–176.2), 192 patients died, with a median OS of 50.2 months. Elderly patients did not show inferior OS (young vs. elderly, 57.7% vs. 54.0% at 3 years, <i>P</i> = 0.247). 71.0% and 87.2% of all patients had low muscle mass before and after NACRT, respectively, which was not associated with OS (<i>P</i> = 0.270 and <i>P</i> = 0.509, respectively). Inflammatory (NLR and PLR) and nutritional index (PNI) values or their changes did not correlate with OS. However, the EML group had worse OS (41.6% vs. 63.2% at 3 years, <i>P</i> < 0.0001). In the multivariate analysis, EML was also a significant prognostic factor for OS. In the subgroup analysis by age, EML was a strong prognostic factor for OS in the elderly group. The 3-year OS was 36.8% in the EML group and 64.9% in the non-EML group (<i>P</i> < 0.0001) in elderly patients, and 47.4% and 62.1% (<i>P</i> = 0.063) in the young patients. In multivariate analysis of each subgroup, EML remained prognostic only in the elderly group (<i>P</i> = 0.008).</p> </section> <section> <h3> Conclusions</h3> <p>EML may be strongly associate
我们旨在确定肌肉质量对接受新辅助化放疗(NACRT)的老年患者局部晚期食管癌(LAEC)的影响。
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引用次数: 0
Effect of sirolimus on muscle in inclusion body myositis observed with magnetic resonance imaging and spectroscopy 通过磁共振成像和光谱学观察西罗莫司对包涵体肌炎患者肌肉的影响
IF 8.9 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-13 DOI: 10.1002/jcsm.13451
Harmen Reyngoudt, Pierre-Yves Baudin, Ericky Caldas de Almeida Araújo, Damien Bachasson, Jean-Marc Boisserie, Kubéraka Mariampillai, Mélanie Annoussamy, Yves Allenbach, Jean-Yves Hogrel, Pierre G. Carlier, Benjamin Marty, Olivier Benveniste
<div> <section> <h3> Background</h3> <p>Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1-year longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (<sup>31</sup>P MRS) in a placebo-controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles.</p> </section> <section> <h3> Methods</h3> <p>Quantitative MRI and <sup>31</sup>P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year-1, and 21 healthy controls. Assessments included fat fraction (FF), contractile cross-sectional area (cCSA), and water T<sub>2</sub> in global leg and thigh segments, muscle groups, individual muscles, as well as <sup>31</sup>P MRS indices in <i>quadriceps</i> or <i>triceps surae</i>. Analyses covered patient-control comparisons, annual change assessments via standard <i>t</i>-tests and linear mixed models, calculation of standardized response means (SRM), and exploration of correlations between MRI, <sup>31</sup>P MRS, functional, strength, and clinical parameters.</p> </section> <section> <h3> Results</h3> <p>The <i>quadriceps</i> and <i>gastrocnemius medialis</i> muscles had the highest FF values, displaying notable heterogeneity and asymmetry, particularly in the <i>quadriceps</i>. In the placebo group, the median 1-year FF increase in the quadriceps was 3.2% (<i>P</i> < 0.001), whereas in the sirolimus group, it was 0.7% (<i>P</i> = 0.033). Both groups experienced a significant decrease in cCSA in the <i>quadriceps</i> after 1 year (<i>P</i> < 0.001), with median changes of 12.6% for the placebo group and 5.5% for the sirolimus group. Differences in FF and cCSA changes between the two groups were significant (<i>P</i> < 0.001). SRM values for FF and cCSA were 1.3 and 1.4 in the placebo group and 0.5 and 0.8 in the sirolimus group, respectively. Water T<sub>2</sub> values were highest in the <i>quadriceps</i> muscles of both groups, significantly exceeding control values in both groups (<i>P</i> < 0.001) and were higher in the placebo group than in the sirolimus group. After treatment, water T<sub>2</sub> increased significantly only in the sirolimus group's <i>quadriceps</i> (<i>P</i> < 0.01). Multiple <sup>31</sup>P MRS indices were abnormal in patients compared to controls and remained unchanged after treatment. Significant correlations were identified between baseline water T<sub>2</sub> and FF at baseline and
在神经肌肉疾病的自然史研究和治疗试验中,寻找敏感的临床结果测量指标已变得至关重要。在这里,我们重点研究了西罗莫司治疗包涵体肌炎(IBM)的安慰剂对照研究中定量磁共振成像(MRI)和磷磁共振波谱(31P MRS)的1年纵向数据,同时还考察了它们与下肢肌肉功能、力量和临床参数的联系。
{"title":"Effect of sirolimus on muscle in inclusion body myositis observed with magnetic resonance imaging and spectroscopy","authors":"Harmen Reyngoudt,&nbsp;Pierre-Yves Baudin,&nbsp;Ericky Caldas de Almeida Araújo,&nbsp;Damien Bachasson,&nbsp;Jean-Marc Boisserie,&nbsp;Kubéraka Mariampillai,&nbsp;Mélanie Annoussamy,&nbsp;Yves Allenbach,&nbsp;Jean-Yves Hogrel,&nbsp;Pierre G. Carlier,&nbsp;Benjamin Marty,&nbsp;Olivier Benveniste","doi":"10.1002/jcsm.13451","DOIUrl":"10.1002/jcsm.13451","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1-year longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (&lt;sup&gt;31&lt;/sup&gt;P MRS) in a placebo-controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Quantitative MRI and &lt;sup&gt;31&lt;/sup&gt;P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year-1, and 21 healthy controls. Assessments included fat fraction (FF), contractile cross-sectional area (cCSA), and water T&lt;sub&gt;2&lt;/sub&gt; in global leg and thigh segments, muscle groups, individual muscles, as well as &lt;sup&gt;31&lt;/sup&gt;P MRS indices in &lt;i&gt;quadriceps&lt;/i&gt; or &lt;i&gt;triceps surae&lt;/i&gt;. Analyses covered patient-control comparisons, annual change assessments via standard &lt;i&gt;t&lt;/i&gt;-tests and linear mixed models, calculation of standardized response means (SRM), and exploration of correlations between MRI, &lt;sup&gt;31&lt;/sup&gt;P MRS, functional, strength, and clinical parameters.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The &lt;i&gt;quadriceps&lt;/i&gt; and &lt;i&gt;gastrocnemius medialis&lt;/i&gt; muscles had the highest FF values, displaying notable heterogeneity and asymmetry, particularly in the &lt;i&gt;quadriceps&lt;/i&gt;. In the placebo group, the median 1-year FF increase in the quadriceps was 3.2% (&lt;i&gt;P&lt;/i&gt; &lt; 0.001), whereas in the sirolimus group, it was 0.7% (&lt;i&gt;P&lt;/i&gt; = 0.033). Both groups experienced a significant decrease in cCSA in the &lt;i&gt;quadriceps&lt;/i&gt; after 1 year (&lt;i&gt;P&lt;/i&gt; &lt; 0.001), with median changes of 12.6% for the placebo group and 5.5% for the sirolimus group. Differences in FF and cCSA changes between the two groups were significant (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). SRM values for FF and cCSA were 1.3 and 1.4 in the placebo group and 0.5 and 0.8 in the sirolimus group, respectively. Water T&lt;sub&gt;2&lt;/sub&gt; values were highest in the &lt;i&gt;quadriceps&lt;/i&gt; muscles of both groups, significantly exceeding control values in both groups (&lt;i&gt;P&lt;/i&gt; &lt; 0.001) and were higher in the placebo group than in the sirolimus group. After treatment, water T&lt;sub&gt;2&lt;/sub&gt; increased significantly only in the sirolimus group's &lt;i&gt;quadriceps&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; &lt; 0.01). Multiple &lt;sup&gt;31&lt;/sup&gt;P MRS indices were abnormal in patients compared to controls and remained unchanged after treatment. Significant correlations were identified between baseline water T&lt;sub&gt;2&lt;/sub&gt; and FF at baseline and ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"15 3","pages":"1108-1120"},"PeriodicalIF":8.9,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140550485","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}
引用次数: 0
Glycative stress inhibits hypertrophy and impairs cell membrane integrity in overloaded mouse skeletal muscle 糖应激抑制超负荷小鼠骨骼肌的肥大并损害细胞膜的完整性
IF 8.9 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-04 DOI: 10.1002/jcsm.13444
Tatsuro Egawa, Takeshi Ogawa, Takumi Yokokawa, Kohei Kido, Ryota Iyama, Haiyu Zhao, Eriko Kurogi, Katsumasa Goto, Tatsuya Hayashi
<div> <section> <h3> Background</h3> <p>Glycative stress, characterized by the formation and accumulation of advanced glycation end products (AGEs) associated with protein glycation reactions, has been implicated in inducing a decline of muscle function. Although the inverse correlation between glycative stress and muscle mass and strength has been demonstrated, the underlying molecular mechanisms are not fully understood. This study aimed to elucidate how glycative stress affects the skeletal muscle, particularly the adaptive muscle response to hypertrophic stimuli and its molecular mechanism.</p> </section> <section> <h3> Methods</h3> <p>Male C57BL/6NCr mice were randomly divided into the following two groups: the bovine serum albumin (BSA)-treated and AGE-treated groups. Mice in the AGE-treated group were intraperitoneally administered AGEs (0.5 mg/g) once daily, whereas those in the BSA-treated group received an equal amount of BSA (0.5 mg/g) as the vehicle control. After 7 days of continuous administration, the right leg plantaris muscle of mice in each group underwent functional overload treatment by synergist ablation for 7 days to induce muscle hypertrophy. In in vitro studies, cultured C2C12 myocytes were treated with AGEs (1 mg/mL) to examine cell adhesion and cell membrane permeability.</p> </section> <section> <h3> Results</h3> <p>Continuous AGE administration increased the levels of fluorescent AGEs, Nε-(carboxymethyl) lysine, and methylglyoxal-derived hydroimidazolone-1 in both plasma and skeletal muscle. Plantaris muscle weight, muscle fibre cross-sectional area, protein synthesis rate, and the number of myonuclei increased with functional overload in both groups; however, the increase was significantly reduced by AGE treatment. Some muscles of AGE-treated mice were destroyed by functional overload. Proteomic analysis was performed to explore the mechanisms of muscle hypertrophy suppression and myofibre destruction by AGEs. When principal component analysis was performed on 4659 data obtained by proteomic analysis, AGE treatment was observed to affect protein expression only in functionally overloaded muscles. Enrichment analysis of the 436 proteins extracted using the K-means method further identified a group of proteins involved in cell adhesion. Consistent with this finding, dystrophin–glycoprotein complex proteins and cell adhesion-related proteins were confirmed to increase with functional overload; however, this was attenuated by AGE treatment. Additionally, the treatment of C2C12 muscle cells with AGEs inhibited their ability to adhere and increased cell membrane permeability.</p> </section>
糖化应激的特点是与蛋白质糖化反应相关的高级糖化终产物(AGEs)的形成和积累,它已被认为会导致肌肉功能下降。虽然糖代谢应激与肌肉质量和力量之间的反相关性已经得到证实,但其潜在的分子机制尚未完全明了。本研究旨在阐明糖应激如何影响骨骼肌,特别是肌肉对肥大刺激的适应性反应及其分子机制。
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引用次数: 0
Administration of adiponectin receptor agonist AdipoRon relieves cancer cachexia by mitigating inflammation in tumour-bearing mice 服用脂肪连接素受体激动剂 AdipoRon 可通过减轻肿瘤小鼠的炎症反应缓解癌症恶病质
IF 8.9 1区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-04-04 DOI: 10.1002/jcsm.13454
Isabelle S. Massart, Axell-Natalie Kouakou, Nathan Pelet, Pascale Lause, Olivier Schakman, Audrey Loumaye, Michel Abou-Samra, Louise Deldicque, Laure B. Bindels, Sonia M. Brichard, Jean-Paul Thissen
<div> <section> <h3> Background</h3> <p>Cancer cachexia is a life-threatening, inflammation-driven wasting syndrome that remains untreatable. Adiponectin, the most abundant adipokine, plays an important role in several metabolic processes as well as in inflammation modulation. Our aim was to test whether administration of AdipoRon (AR), a synthetic agonist of the adiponectin receptors, prevents the development of cancer cachexia and its related muscle atrophy.</p> </section> <section> <h3> Methods</h3> <p>The effect of AR on cancer cachexia was investigated in two distinct murine models of colorectal cancer. First, 7-week-old CD2F1 male mice were subcutaneously injected with colon-26 carcinoma cells (C26) or vehicle (CT). Six days after injection, mice were treated for 5 days with AdipoRon (50 mg/kg/day; C26 + AR) or the corresponding vehicle (CT and C26). Additionally, a genetic model, the Apc<sup><i>Min</i>/+</sup> mouse, that develops spontaneously numerous intestinal polyps, was used. Eight-week-old male Apc<sup><i>Min/+</i></sup> mice were treated with AdipoRon (50 mg/kg/day; Apc + AR) or the corresponding vehicle (Apc) over a period of 12 weeks, with C57BL/6J wild-type mice used as controls. In both models, several parameters were assessed in vivo: body weight, grip strength and serum parameters, as well as ex vivo: molecular changes in muscle, fat and liver.</p> </section> <section> <h3> Results</h3> <p>The protective effect of AR on cachexia development was observed in both cachectic C26 and Apc<sup><i>Min</i>/+</sup> mice. In these mice, AR administration led to a significant alleviation of body weight loss and muscle wasting, together with rescued muscle strength (<i>P</i> < 0.05 for all). In both models, AR had a strong anti-inflammatory effect, reflected by lower systemic interleukin-6 levels (−55% vs. C26, <i>P</i> < 0.001 and −80% vs. Apc mice, <i>P</i> < 0.05), reduced muscular inflammation as indicated by lower levels of <i>Socs3</i>, phospho-STAT3 and <i>Serpina3n</i>, an acute phase reactant (<i>P</i> < 0.05 for all). In addition, AR blunted circulating levels of corticosterone (−46% vs. C26 mice, <i>P</i> < 0.001 and −60% vs. Apc mice, <i>P</i> < 0.05), the predominant murine glucocorticoid known to induce muscle atrophy. Accordingly, key glucocorticoid-responsive factors implicated in atrophy programmes were—or tended to be—significantly blunted in skeletal muscle by AR. Finally, AR protected against lipid metabolism alterations observed in Apc<sup><i>Min</i>/+</sup> mice, as it mitigated the increase in circulating triglyceride levels (−38%, <i>P</i> < 0.05) by attenuating hepatic triglyceride synthesis and
背景癌症恶病质是一种危及生命、由炎症引起的消瘦综合征,目前仍无法治疗。脂联素是最丰富的脂肪因子,在多个代谢过程和炎症调节中发挥着重要作用。我们的目的是测试服用脂肪连接素受体的合成激动剂 AdipoRon(AR)是否能预防癌症恶病质的发生及其相关的肌肉萎缩。首先,给 7 周大的 CD2F1 雄性小鼠皮下注射结肠-26 癌细胞(C26)或载体(CT)。注射六天后,用 AdipoRon(50 毫克/公斤/天;C26 + AR)或相应的载体(CT 和 C26)治疗小鼠 5 天。此外,我们还使用了一种自发性多发性肠息肉的遗传模型 ApcMin/+ 小鼠。八周大的雄性 ApcMin/+ 小鼠接受 AdipoRon(50 毫克/千克/天;Apc + AR)或相应的药物(Apc)治疗,为期 12 周,C57BL/6J 野生型小鼠作为对照。在这两种模型中,都对体内参数(体重、握力和血清参数)和体外参数(肌肉、脂肪和肝脏的分子变化)进行了评估。在这些小鼠中,服用 AR 能显著缓解体重下降和肌肉萎缩,并能增强肌肉力量(所有小鼠的 P 均为 0.05)。在这两种模型中,AR 都有很强的抗炎作用,表现为全身白细胞介素-6 水平降低(与 C26 相比降低 55%,P< 0.001;与 Apc 小鼠相比降低 80%,P< 0.05),Socs3、phospho-STAT3 和 Serpina3n(一种急性时相反应物)水平降低,表明肌肉炎症减轻(P< 0.05)。此外,AR 还降低了循环中的皮质酮水平(与 C26 小鼠相比降低了 46%,P < 0.001;与 Apc 小鼠相比降低了 60%,P < 0.05),而皮质酮是已知会诱导肌肉萎缩的主要小鼠糖皮质激素。因此,与肌肉萎缩计划有关的关键糖皮质激素反应因子在骨骼肌中被AR显著减弱或趋于减弱。最后,AR 对 ApcMin/+ 小鼠中观察到的脂质代谢改变具有保护作用,因为它通过抑制肝脏甘油三酯合成和肝脏对脂肪酸的吸收,减轻了循环甘油三酯水平的增加(-38%,P <0.05)。结论总之,这些结果表明,AdipoRon 在临床前小鼠模型中通过减轻体重下降和肌肉萎缩,以及抑制炎症和皮质功能亢进,挽救了糜烂表型。因此,AdipoRon 可以代表一种对抗癌症恶病质的创新治疗策略。
{"title":"Administration of adiponectin receptor agonist AdipoRon relieves cancer cachexia by mitigating inflammation in tumour-bearing mice","authors":"Isabelle S. Massart,&nbsp;Axell-Natalie Kouakou,&nbsp;Nathan Pelet,&nbsp;Pascale Lause,&nbsp;Olivier Schakman,&nbsp;Audrey Loumaye,&nbsp;Michel Abou-Samra,&nbsp;Louise Deldicque,&nbsp;Laure B. Bindels,&nbsp;Sonia M. Brichard,&nbsp;Jean-Paul Thissen","doi":"10.1002/jcsm.13454","DOIUrl":"10.1002/jcsm.13454","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cancer cachexia is a life-threatening, inflammation-driven wasting syndrome that remains untreatable. Adiponectin, the most abundant adipokine, plays an important role in several metabolic processes as well as in inflammation modulation. Our aim was to test whether administration of AdipoRon (AR), a synthetic agonist of the adiponectin receptors, prevents the development of cancer cachexia and its related muscle atrophy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The effect of AR on cancer cachexia was investigated in two distinct murine models of colorectal cancer. First, 7-week-old CD2F1 male mice were subcutaneously injected with colon-26 carcinoma cells (C26) or vehicle (CT). Six days after injection, mice were treated for 5 days with AdipoRon (50 mg/kg/day; C26 + AR) or the corresponding vehicle (CT and C26). Additionally, a genetic model, the Apc&lt;sup&gt;&lt;i&gt;Min&lt;/i&gt;/+&lt;/sup&gt; mouse, that develops spontaneously numerous intestinal polyps, was used. Eight-week-old male Apc&lt;sup&gt;&lt;i&gt;Min/+&lt;/i&gt;&lt;/sup&gt; mice were treated with AdipoRon (50 mg/kg/day; Apc + AR) or the corresponding vehicle (Apc) over a period of 12 weeks, with C57BL/6J wild-type mice used as controls. In both models, several parameters were assessed in vivo: body weight, grip strength and serum parameters, as well as ex vivo: molecular changes in muscle, fat and liver.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The protective effect of AR on cachexia development was observed in both cachectic C26 and Apc&lt;sup&gt;&lt;i&gt;Min&lt;/i&gt;/+&lt;/sup&gt; mice. In these mice, AR administration led to a significant alleviation of body weight loss and muscle wasting, together with rescued muscle strength (&lt;i&gt;P&lt;/i&gt; &lt; 0.05 for all). In both models, AR had a strong anti-inflammatory effect, reflected by lower systemic interleukin-6 levels (−55% vs. C26, &lt;i&gt;P&lt;/i&gt; &lt; 0.001 and −80% vs. Apc mice, &lt;i&gt;P&lt;/i&gt; &lt; 0.05), reduced muscular inflammation as indicated by lower levels of &lt;i&gt;Socs3&lt;/i&gt;, phospho-STAT3 and &lt;i&gt;Serpina3n&lt;/i&gt;, an acute phase reactant (&lt;i&gt;P&lt;/i&gt; &lt; 0.05 for all). In addition, AR blunted circulating levels of corticosterone (−46% vs. C26 mice, &lt;i&gt;P&lt;/i&gt; &lt; 0.001 and −60% vs. Apc mice, &lt;i&gt;P&lt;/i&gt; &lt; 0.05), the predominant murine glucocorticoid known to induce muscle atrophy. Accordingly, key glucocorticoid-responsive factors implicated in atrophy programmes were—or tended to be—significantly blunted in skeletal muscle by AR. Finally, AR protected against lipid metabolism alterations observed in Apc&lt;sup&gt;&lt;i&gt;Min&lt;/i&gt;/+&lt;/sup&gt; mice, as it mitigated the increase in circulating triglyceride levels (−38%, &lt;i&gt;P&lt;/i&gt; &lt; 0.05) by attenuating hepatic triglyceride synthesis and","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"15 3","pages":"919-933"},"PeriodicalIF":8.9,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349310","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}
引用次数: 0
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Journal of Cachexia Sarcopenia and Muscle
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