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BACKGROUND: While body mass index (BMI) is the most widely used indicator as a measure of obesity factors in post-transplantation diabetes mellitus (PTDM), body composition is a more accurate measure of obesity. This study aims to investigate the effects of Computed tomography (CT)--based morphemic factors on PTDM and establish a prediction model for PTDM after kidney transplantation. METHODS: The pre-transplant data and glycemic levels of kidney transplant recipients (June 2021 to July 2023) were retrospectively and prospectively collected. Univariate and multivariate analyses were conducted to analyze the relationship between morphemic factors and PTDM at one month, six months, and one year after hospital discharge. Subsequently, a one-year risk prediction model based on morphemic factors was developed. RESULTS: The study consisted of 131 participants in the one-month group, where Hemoglobin A1c (HbA1c) (p = 0.02) was identified as the risk factor for PTDM. In the six-month group, 129 participants were included, and the intermuscular adipose tissue (IMAT) area (p = 0.02) was identified as the risk factor for PTDM. The one-year group had 128 participants, and the risk factors for PTDM were identified as body mass index (BMI) (p = 0.02), HbA1c (p = 0.01), and IMAT area (p = 0.007). HbA1c (%) and IMAT area were included in the risk prediction Model for PTDM in the one-year group with AUC = 0.716 (95 % CI 0.591-0.841, p = 0.001). CONCLUSIONS: Compared to BMI and other morphemic factors, this study demonstrated that the IMAT area was the most potential predictor of PTDM. CLINICAL TRIAL NOTATION: Chictr.org (ChiCTR2300078639).

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Given the critical role of skeletal muscle in healthy aging, low muscle mass (myopenia) and quality (myosteatosis) can be used as predictors of poor functional and cardiometabolic outcomes. Myopenia is also a part of sarcopenia and malnutrition diagnostic criteria. However, there is limited evidence for using chest computed tomography (CT) to evaluate muscle health. We aimed to compare chest CT landmarks to the widely used L3 vertebra for single-slice skeletal muscle evaluation in patients with heart failure (HF). Patients admitted for acute decompensated HF between January 2017 and December 2018 were retrospectively analyzed. Body composition measurements were made on CT of the chest and abdomen/pelvis with or without contrast one month before discharge. Skeletal muscle index (SMI) and intermuscular adipose tissue percentage (IMAT%) were calculated at several thoracic levels (above the aortic arch, T8, and T12) and correlated to the widely used L3 level. A total of 200 patients were included, 89 (44.5%) female. The strongest correlation of thoracic SMI (for muscle quantity) and IMAT% (for muscle quality) with L3 was at the T12 level (r = 0.834, p < 0.001 and r = 0.757, p < 0.001, respectively). Cutoffs to identify low muscle mass for T12 SMI (derived from the lowest sex-stratified L3 SMI tertile) were 31.1 cm²/m² in men and 26.3 cm²/m² in women. SMI and IMAT% at T12 had excellent correlations with the widely used L3 level for muscle quantity and quality evaluation in patients with HF.

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Insuficiencia Cardíaca , Músculo Esquelético , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/fisiopatología , Sarcopenia/diagnóstico por imagen , Sarcopenia/fisiopatología , Anciano de 80 o más Años , Puntos Anatómicos de Referencia , Radiografía Torácica , Reproducibilidad de los Resultados , Adiposidad , Composición Corporal

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BACKGROUND AND AIMS: High tissue sodium accumulation and intermuscular adipose tissue (IMAT) are associated with aging, type 2 diabetes, and chronic kidney disease. In this study, we aim to investigate whether high lower-extremity tissue sodium accumulation relates to IMAT quantity and whether systemic inflammatory mediators and adipocytokines contribute to such association. METHODS: Tissue sodium content and IMAT accumulation (percentage of IMAT area to muscle area) were measured in 83 healthy individuals using sodium imaging (23Na-MRI) and proton (1H-MRI) imaging of the calf. Insulin sensitivity was assessed by glucose disposal rate (GDR) measured with the hyperinsulinemic-euglycemic clamp. RESULTS: Median (interquartile range) muscle and skin sodium contents were 16.6 (14.9, 19.0) and 12.6 (10.9, 16.7) mmol/L, respectively. Median IMAT was 3.69 (2.80, 5.37) %. In models adjusted for age, sex, BMI, GDR, adiponectin, and high-sensitivity C-reactive protein, increasing tissue sodium content was significantly associated with higher IMAT quantity (p = 0.018 and 0.032 for muscle and skin tissue sodium, respectively). In subgroup analysis stratified by sex, skin sodium was significantly associated with IMAT only among men. In interaction analysis, the association between skin sodium and IMAT was greater with increasing levels of high-sensitivity C-reactive protein and interleukin-6 (p for interaction = 0.022 and 0.006, respectively). CONCLUSIONS: Leg muscle and skin sodium are associated with IMAT quantity among healthy individuals. The relationship between skin sodium and IMAT may be mediated by systemic inflammation.

Asunto(s)

Tejido Adiposo , Músculo Esquelético , Sodio , Humanos , Masculino , Femenino , Tejido Adiposo/metabolismo , Tejido Adiposo/diagnóstico por imagen , Adulto , Sodio/metabolismo , Músculo Esquelético/metabolismo , Persona de Mediana Edad , Piel/metabolismo , Resistencia a la Insulina , Imagen por Resonancia Magnética/métodos

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BACKGROUND & AIMS: Accurate diagnosis of sarcopenia requires evaluation of muscle quality, which refers to the amount of fat infiltration in muscle tissue. In this study, we aim to investigate whether we can independently predict mortality risk in transcatheter aortic valve implantation (TAVI) patients, using automatic deep learning algorithms to assess muscle quality on procedural computed tomography (CT) scans. METHODS: This study included 1199 patients with severe aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) between January 2010 and January 2020. A procedural CT scan was performed as part of the preprocedural-TAVI evaluation, and the scans were analyzed using deep-learning-based software to automatically determine skeletal muscle density (SMD) and intermuscular adipose tissue (IMAT). The association of SMD and IMAT with all-cause mortality was analyzed using a Cox regression model, adjusted for other known mortality predictors, including muscle mass. RESULTS: The mean age of the participants was 80 ± 7 years, 53% were female. The median observation time was 1084 days, and the overall mortality rate was 39%. We found that the lowest tertile of muscle quality, as determined by SMD, was associated with an increased risk of mortality (HR 1.40 [95%CI: 1.15-1.70], p < 0.01). Similarly, low muscle quality as defined by high IMAT in the lowest tertile was also associated with increased mortality risk (HR 1.24 [95%CI: 1.01-1.52], p = 0.04). CONCLUSIONS: Our findings suggest that deep learning-assessed low muscle quality, as indicated by fat infiltration in muscle tissue, is a practical, useful and independent predictor of mortality after TAVI.

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BACKGROUND: Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. METHODS: This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. RESULTS: The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p < 0.001). Age (r = - 0.411, p < 0.001), IMAT % (r = - 0.424, p < 0.001), negatively associated with FACIT-F score. Multivariate logistic regression analysis shows that older age, lower serum phosphorus, higher IMAT% are associated with a high risk of fatigue. CONCLUSION: The significantly increased incidence and degree of fatigue in hemodialysis patients is associated with more intermuscular adipose tissue in paraspinal muscle.

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Composición Corporal , Fatiga , Fuerza Muscular , Diálisis Renal , Humanos , Diálisis Renal/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Fatiga/fisiopatología , Fatiga/etiología , Estudios Transversales , Fuerza Muscular/fisiología , Anciano , Fuerza de la Mano/fisiología , Densidad Ósea , Adulto , Músculo Esquelético/fisiopatología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/fisiopatología

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Introduction: Magnetic resonance imaging (MRI) enables direct measurements of muscle volume and quality, allowing for an in-depth understanding of their associations with anthropometric traits, and health conditions. However, it is unclear which muscle volume measurements: total muscle volume, regional measurements, measurements of muscle quality: intermuscular adipose tissue (IMAT) or proton density fat fraction (PDFF), are most informative and associate with relevant health conditions such as dynapenia and frailty. Methods: We have measured image-derived phenotypes (IDPs) including total and regional muscle volumes and measures of muscle quality, derived from the neck-to-knee Dixon images in 44,520 UK Biobank participants. We further segmented paraspinal muscle from 2D quantitative MRI to quantify muscle PDFF and iron concentration. We defined dynapenia based on grip strength below sex-specific cut-off points and frailty based on five criteria (weight loss, exhaustion, grip strength, low physical activity and slow walking pace). We used logistic regression to investigate the association between muscle volume and quality measurements and dynapenia and frailty. Results: Muscle volumes were significantly higher in male compared with female participants, even after correcting for height while, IMAT (corrected for muscle volume) and paraspinal muscle PDFF were significantly higher in female compared with male participants. From the overall cohort, 7.6% (N = 3,261) were identified with dynapenia, and 1.1% (N = 455) with frailty. Dynapenia and frailty were positively associated with age and negatively associated with physical activity levels. Additionally, reduced muscle volume and quality measurements were associated with both dynapenia and frailty. In dynapenia, muscle volume IDPs were most informative, particularly total muscle exhibiting odds ratios (OR) of 0.392, while for frailty, muscle quality was found to be most informative, in particular thigh IMAT volume indexed to height squared (OR = 1.396), both with p-values below the Bonferroni-corrected threshold (p<8.8×10-5). Conclusion: Our fully automated method enables the quantification of muscle volumes and quality suitable for large population-based studies. For dynapenia, muscle volumes particularly those including greater body coverage such as total muscle are the most informative, whilst, for frailty, markers of muscle quality were the most informative IDPs. These results suggest that different measurements may have varying diagnostic values for different health conditions.

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BACKGROUND: GrimAge acceleration (GAA), an epigenetic marker that represents physiologic aging, is associated with age-related diseases including cancer and cardiovascular diseases. However, the associations between GAA and muscle mass and function are unknown. METHODS: We estimated measures of GAA in 1 118 Black and White participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study at exam years (Y) 15 (2000-2001) and 20 (2005-2006). Abdominal muscle composition was measured using CT scans at the Y25 (2010-2011) visit. We used multivariate regression models to examine associations of GAA estimates with muscle imaging measurements. RESULTS: In the CARDIA study, each 1-year higher GAA was associated with an average 1.1% (95% confidence interval [CI]: 0.6%, 1.5%) higher intermuscular adipose tissue (IMAT) volume for abdominal muscles. Each 1-year higher GAA was associated with an average -0.089 Hounsfield unit (HU; 95% CI: -0.146, -0.032) lower lean muscle attenuation and an average -0.049 HU (95% CI: -0.092, -0.007) lower IMAT attenuation for abdominal muscles. Stratified analyses showed that GAA was more strongly associated with higher abdominal muscle IMAT volume in females and significantly associated with lower lean muscle attenuation for White participants only. CONCLUSIONS: Higher GAA is associated with higher abdominal muscle IMAT volume and lower lean muscle attenuation in a midlife population.

Asunto(s)

Grasa Abdominal , Vasos Coronarios , Femenino , Humanos , Músculos , Envejecimiento/genética , Epigénesis Genética , Músculo Esquelético/diagnóstico por imagen

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Intermuscular adipose tissue (IMAT) is a unique adipose depot interspersed between muscle fibers (myofibers) or muscle groups. Numerous studies have shown that IMAT is strongly associated with insulin resistance and muscular dysfunction in people with metabolic disease, such as obesity and type 2 diabetes. Moreover, IMAT aggravates obesity-related muscle metabolism disorders via secretory factors. Interestingly, researchers have discovered that intermuscular brown adipocytes in rodent models provide new hope for obesity treatment by acting on energy dissipation, which inspired researchers to explore the underlying regulation of IMAT formation. However, the molecular and cellular properties and regulatory processes of IMAT remain debated. Previous studies have suggested that muscle-derived stem/progenitor cells and other adipose tissue progenitors contribute to the development of IMAT. Adipocytes within IMAT exhibit features that are similar to either white adipocytes or uncoupling protein 1 (UCP1)-positive brown adipocytes. Additionally, given the heterogeneity of skeletal muscle, which comprises myofibers, satellite cells, and resident mesenchymal progenitors, it is plausible that interplay between these cellular components actively participate in the regulation of intermuscular adipogenesis. In this context, we review recent studies associated with IMAT to offer insights into the cellular origins, biological properties, and regulatory mechanisms of IMAT. Our aim is to provide novel ideas for the therapeutic strategy of IMAT and the development of new drugs targeting IMAT-related metabolic diseases.

Asunto(s)

Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Tejido Adiposo/metabolismo , Obesidad/metabolismo , Músculo Esquelético/metabolismo , Adipocitos Blancos/metabolismo

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As age increases, adipose tissue infiltrates muscle tissue and leads to sarcopenia. When excessive accumulation of adipose tissue accompanied progressive decrease in lean body mass especially visceral fat, termed as sarcopenic obesity (SO) and related metabolic intermuscular adipose tissue (IMAT) is an ectopic tissue found between muscle groups, and is distinct from subcutaneous adipose tissue. Until now, the association between IMAT and metabolic health was not understood. This study is the first systematic review assessing the association between IMAT and metabolic health. The PubMed, Science Direct and Cochrane databases were searched for studies reporting IMAT and metabolic risk. The descriptions of the extracted data are guided by the Preferred Reporting Items for Systematic Reviews (PRISMA) statement with a Grading of Recommendations Assessment, Development and Evaluation approach. This study is registered at PROSPERO (identifier: CRD42022337518). Six studies were pooled and reviewed using critical appraisal by the Newcastle Ottawa Scale and Centre for Evidence-Based Medicine checklist. Two clinical trials and four observational trials were included. Our results reveal that IMAT is associated with metabolic risk, especially in older adults and patients with obesity. However, in a person with abdominal obesity, VAT has a more significant role in metabolic risk than IMAT. The largest decrease in IMAT was achieved by combining aerobic with resistance training.

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AIMS/HYPOTHESIS: Although insulin resistance often leads to type 2 diabetes mellitus, its early stages are often unrecognised, thus reducing the probability of successful prevention and intervention. Moreover, treatment efficacy is affected by the genetics of the individual. We used gene expression profiles from a cross-sectional study to identify potential candidate genes for the prediction of diabetes risk and intervention response. METHODS: Using a multivariate regression model, we linked gene expression profiles of human skeletal muscle and intermuscular adipose tissue (IMAT) to fasting glucose levels and glucose infusion rate. Based on the expression patterns of the top predictive genes, we characterised and compared individual gene expression with clinical classifications using k-nearest neighbour clustering. The predictive potential of the candidate genes identified was validated using muscle gene expression data from a longitudinal intervention study. RESULTS: We found that genes with a strong association with clinical measures clustered into three distinct expression patterns. Their predictive values for insulin resistance varied substantially between skeletal muscle and IMAT. Moreover, we discovered that individual gene expression-based classifications may differ from classifications based predominantly on clinical variables, indicating that participant stratification may be imprecise if only clinical variables are used for classification. Of the 15 top candidate genes, ST3GAL2, AASS, ARF1 and the transcription factor SIN3A are novel candidates for predicting a refined diabetes risk and intervention response. CONCLUSION/INTERPRETATION: Our results confirm that disease progression and successful intervention depend on individual gene expression states. We anticipate that our findings may lead to a better understanding and prediction of individual diabetes risk and may help to develop individualised intervention strategies.

Asunto(s)

Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Resistencia a la Insulina/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Pronóstico , Estudios Transversales , Músculo Esquelético/metabolismo , Obesidad/metabolismo , Tejido Adiposo/metabolismo , Glucosa/metabolismo , Biomarcadores/metabolismo , Perfilación de la Expresión Génica

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Altered mitochondrial quality and function in muscle may be involved in age-related physical function decline. The role played by the autophagy-lysosome system, a major component of mitochondrial quality control (MQC), is incompletely understood. This study was undertaken to obtain initial indications on the relationship between autophagy, mitophagy, and lysosomal markers in muscle and measures of physical performance and lower extremity tissue composition in young and older adults. Twenty-three participants were enrolled, nine young (mean age: 24.3 ± 4.3 years) and 14 older adults (mean age: 77.9 ± 6.3 years). Lower extremity tissue composition was quantified volumetrically by magnetic resonance imaging and a tissue composition index was calculated as the ratio between muscle and intermuscular adipose tissue volume. Physical performance in older participants was assessed via the Short Physical Performance Battery (SPPB). Protein levels of the autophagy marker p62, the mitophagy mediator BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), the lysosomal markers transcription factor EB, vacuolar-type ATPase, and lysosomal-associated membrane protein 1 were measured by Western immunoblotting in vastus lateralis muscle biopsies. Older adults had smaller muscle volume and lower tissue composition index than young participants. The protein content of p62 and BNIP3 was higher in older adults. A negative correlation was detected between p62 and BNIP3 and the tissue composition index. p62 and BNIP3 were also related to the performance on the 5-time sit-to-stand test of the SPPB. Our results suggest that an altered expression of markers of the autophagy/mitophagy-lysosomal system is related to deterioration of lower extremity tissue composition and muscle dysfunction. Additional studies are needed to clarify the role of defective MQC in human muscle aging and identify novel biological targets for drug development.

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Mitocondrias , Músculo Esquelético , Humanos , Anciano , Adulto Joven , Adulto , Anciano de 80 o más Años , Músculo Esquelético/metabolismo , Mitocondrias/metabolismo , Envejecimiento/fisiología , Extremidad Inferior , Rendimiento Físico Funcional

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ß-Hydroxy-ß-methylbutyrate (HMB), a leucine metabolite, can increase skeletal muscle size and function. However, HMB may be less effective at improving muscle function in people with insufficient Vitamin D3 (25-OH-D < 30 ng/mL) which is common in middle-aged and older adults. Therefore, we tested the hypothesis that combining HMB plus Vitamin D3 (HMB + D) supplementation would improve skeletal muscle size, composition, and function in middle-aged women. In a double-blinded fashion, women (53 ± 1 yrs, 26 ± 1 kg/m2, n = 43) were randomized to take placebo or HMB + D (3 g Calcium HMB + 2000 IU D per day) during 12 weeks of sedentary behavior (SED) or resistance exercise training (RET). On average, participants entered the study Vitamin D3 insufficient while HMB + D increased 25-OH-D to sufficient levels after 8 and 12 weeks. In SED, HMB + D prevented the loss of arm lean mass observed with placebo. HMB + D increased muscle volume and decreased intermuscular adipose tissue (IMAT) volume in the thigh compared to placebo but did not change muscle function. In RET, 12-weeks of HMB + D decreased IMAT compared to placebo but did not influence the increase in skeletal muscle volume or function. In summary, HMB + D decreased IMAT independent of exercise status and may prevent the loss or increase muscle size in a small cohort of sedentary middle-aged women. These results lend support to conduct a longer duration study with greater sample size to determine the validity of the observed positive effects of HMB + D on IMAT and skeletal muscle in a small cohort of middle-aged women.

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Colecalciferol , Fuerza Muscular , Humanos , Persona de Mediana Edad , Femenino , Anciano , Colecalciferol/farmacología , Suplementos Dietéticos , Músculo Esquelético , Método Doble Ciego

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Backgrounds: The patient-generated subjective global assessment (PG-SGA) is one of the screening criteria for malnutrition, the skeletal muscle radiodensity (SMD) and skeletal muscle mass index (SMI) are associated with survival in colorectal cancer patients. Body composition parameters can be easily assessed; however, few studies have examined the association between total muscle wasting scores in PG-SGA and body composition parameters and two muscle abnormalities. Methods: This cohort study included 1,637 stage I-III CRC patients from 2 clinical centers in China, who were enrolled in the training cohort (n = 1,005) and validation cohort (n = 632). Baseline data were collected prospectively from patients including age, BMI, staging, gait speed, hand grip strength (HGS), peak expiratory flow (PEF), neutrophil-lymphocyte ratio (NLR), intermuscular adipose tissue (IMAT), visceral fat area (VFA) and total muscle wasting score in PG-SGA. Relevant risk factors were subjected to logistic regression analysis and Cox regression analysis to identify characteristics associated with muscle abnormalities and survival. Based on the logistic model results, normograms were established to predict muscle abnormalities, and its discrimination and calibration were assessed using the receiver operating characteristic (ROC) curve and calibration curve. The Kaplan-Meier curves were used to assess the survival of colorectal cancer patients with malnutrition or sarcopenia in an inflammatory state (assessed by NLR). Results: The mean age of all participants was 57.7 ± 10.6 years (56.9% males) and the prevalence of low SMD and low SMI was 32.2 and 39.5%, respectively. Low SMD rate was significantly associated with age, TNM stage, BMI, IMAT, walking speed, total muscle wasting score and NRS2002 score by logistic regression analysis (p < 0.05). Low SMI rate was significantly correlated with age, NLR, BMI, PEF, handgrip strength, calf circumference, walking speed, total muscle wasting score and NRS2002 score (p < 0.05). The AUCs of the diagnostic nomograms were 0.859 (95% CI, 0.831-0.886) for low SMD and 0.843 (95% CI, 0.813-0.871) for low SMI in the validation cohort. We also found that patients with colorectal cancer with malnutrition or sarcopenia had a worse prognosis when NLR ≥3.5. Conclusion: Muscle abnormalities and malnutrition are strongly associated with mortality in patients with non-metastatic colorectal cancer. Early identification and intervention of the associated risk factors may offer new ways to improve patient prognosis.

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Chemotherapy is a common therapy to treat patients with breast cancer but also leads to skeletal muscle deconditioning. Skeletal muscle deconditioning is multifactorial and intermuscular adipose tissue (IMAT) accumulation is closely linked to muscle dysfunction. To date, there is no clinical study available investigating IMAT development through a longitudinal protocol and the underlying mechanisms remain unknown. Our study was dedicated to investigating IMAT content in patients with early breast cancer who were treated with chemotherapy and exploring the subsequent cellular mechanisms involved in its development. We included 13 women undergoing chemotherapy. Muscle biopsies and ultrasonography assessment were performed before and after chemotherapy completion. Histological and Western blotting analyses were conducted. We found a substantial increase in protein levels of three mature adipocyte markers (perilipin, +901%; adiponectin, +135%; FABP4, +321%; P < 0.05). These results were supported by an increase in oil red O-positive staining (+358%; P < 0.05). A substantial increase in PDGFRα protein levels was observed (+476%; P < 0.05) highlighting an increase in fibro-adipogenic progenitors (FAPs) content. The cross-sectional area of the vastus lateralis muscle fibers substantially decreased (-21%; P < 0.01), and muscle architecture was altered, as shown by a decrease in fascicle length (-15%; P < 0.05) and a decreasing trend in muscle thickness (-8%; P = 0.08). We demonstrated both IMAT development and muscle atrophy in patients with breast cancer who were treated with chemotherapy. FAPs, critical stem cells inducing both IMAT development and skeletal muscle atrophy, also increased, suggesting that FAPs likely play a critical role in the skeletal muscle deconditioning observed in patients with breast cancer who were treated with chemotherapy.

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Neoplasias de la Mama , Adiponectina/metabolismo , Tejido Adiposo/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Músculo Esquelético/metabolismo , Atrofia Muscular/inducido químicamente , Atrofia Muscular/diagnóstico por imagen , Atrofia Muscular/metabolismo , Perilipinas/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo

RESUMEN

Besides the loss of muscle mass and strength, increased intermuscular adipose tissue (IMAT) is now a well-recognized consequence of muscle deconditioning as experienced in prolonged microgravity. IMAT content may alter the muscle stem cell microenvironment. We hypothesized that extracellular matrix structure alterations and microenvironment remodeling induced by fast and severe muscle disuse could modulate fibro-adipogenic progenitor fate and behavior. We used the dry immersion (DI) model that rapidly leads to severe muscle deconditioning due to drastic hypoactivity. We randomly assigned healthy volunteers (n = 18 men) to the control group (only DI, n = 9; age = 33.8 ± 4) or to the DI + thigh cuff group (n = 9; age = 33.4 ± 7). Participants remained immersed in the supine position in a thermo-neutral water bath for 5 days. We collected vastus lateralis biopsies before (baseline) and after DI. 5 days of DI are sufficient to reduce muscle mass significantly, as indicated by the decreased myofiber cross-sectional area in vastus lateralis samples (−18% vs. baseline, p < 0.05). Early and late adipogenic differentiation transcription factors protein levels were upregulated. Platelet-derived growth Factors alpha (PDGFR⍺) protein level and PDGFR⍺-positive cells were increased after 5 days of DI. Extracellular matrix structure was prone to remodeling with an altered ECM composition with 4 major collagens, fibronectin, and Connective Tissue Growth Factor mRNA decreases (p < 0.001 vs. baseline). Wearing thigh cuffs did not have any preventive effect on the measured variable. Our results show that altered extracellular matrix structure and signaling pathways occur early during DI, a severe muscle wasting model, favoring fibro-adipogenic progenitor differentiation into adipocytes.

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Adipocitos , Músculo Esquelético , Adipogénesis/fisiología , Adulto , Diferenciación Celular/fisiología , Matriz Extracelular , Humanos , Masculino , Músculo Esquelético/metabolismo

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Intermuscular adipose tissue (IMAT) is an ectopic fat depot found beneath the fascia and within the muscles. IMAT modulates muscle insulin sensitivity and triggers local and systemic chronic low-grade inflammation by producing cytokines and chemokines, which underlie the pathogenesis of Type 2 diabetes mellitus (T2DM). Imaging techniques have been increasingly used to non-invasively quantify IMAT in patients with diabetes in research and healthcare settings. In this study, we systematically reviewed the cell of origin and definition of IMAT, and the use of quantitative and functional imaging technology pertinent to the etiology, risk factors, lifestyle modification, and therapeutic treatment of diabetes. The purpose of this article is to provide important insight into the current understanding of IMAT and future prospects of targeting IMAT for T2DM control.

Asunto(s)

Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Tejido Adiposo/diagnóstico por imagen , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/patología , Humanos , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología

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Worldwide prevalence of obesity is associated with the increase of lifestyle-related diseases. The accumulation of intermuscular adipose tissue (IMAT) is considered a major problem whereby obesity leads to sarcopenia and metabolic disorders and thus is a promising target for treating these pathological conditions. However, whereas obesity-associated IMAT is suggested to originate from PDGFRα+ mesenchymal progenitors, the processes underlying this adipogenesis remain largely unexplored. Here, we comprehensively investigated intra- and extracellular changes associated with these processes using single-cell RNA sequencing and mass spectrometry. Our single-cell RNA sequencing analysis identified a small PDGFRα+ cell population in obese mice directed strongly toward adipogenesis. Proteomic analysis showed that the appearance of this cell population is accompanied by an increase in galectin-3 in interstitial environments, which was found to activate adipogenic PPARγ signals in PDGFRα+ cells. Moreover, IMAT formation during muscle regeneration was significantly suppressed in galectin-3 knockout mice. Our findings, together with these multi-omics datasets, could unravel microenvironmental networks during muscle regeneration highlighting possible therapeutic targets against IMAT formation in obesity.

Asunto(s)

Tejido Adiposo/metabolismo , Galectina 3/metabolismo , Músculo Esquelético/fisiología , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Actinas/genética , Actinas/metabolismo , Adipogénesis , Tejido Adiposo/citología , Animales , Cardiotoxinas/farmacología , Diferenciación Celular , Senescencia Celular/genética , Dieta Alta en Grasa , Femenino , Galectina 3/deficiencia , Galectina 3/genética , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Obesidad/metabolismo , Obesidad/patología , PPAR gamma/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/deficiencia , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Regeneración , Transducción de Señal/genética

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In physiological conditions, the adipose organ resides in well-defined areas, where it acts providing an energy supply and as an endocrine organ involved in the control of whole-body energy metabolism. Adipose tissue adipokines connect the body's nutritional status to the regulation of energy balance. When it surrounds organs, it provides also for mechanical protection. Adipose tissue has a complex and heterogenous cellular composition that includes adipocytes, adipose tissue-derived stromal and stem cells (ASCs) which are mesenchymal stromal cells, and endothelial and immune cells, which signal to each other and to other tissues to maintain homeostasis. In obesity and in other nutrition related diseases, as well as in age-related diseases, biological and functional changes of adipose tissue give rise to several complications. Obesity triggers alterations of ASCs, impairing adipose tissue remodeling and adipose tissue function, which induces low-grade systemic inflammation, progressive insulin resistance and other metabolic disorders. Adipose tissue grows by hyperplasia recruiting new ASCs and by hypertrophy, up to its expandability limit. To overcome this limitation and to store the excess of nutrients, adipose tissue develops ectopically, involving organs such as muscle, bone marrow and the heart. The origin of ectopic adipose organ is not clearly elucidated, and a possible explanation lies in the stimulation of the adipogenic differentiation of mesenchymal precursor cells which normally differentiate toward a lineage specific for the organ in which they reside. The chronic exposition of these newly-formed adipose depots to the pathological environment, will confer to them all the phenotypic characteristics of a dysfunctional adipose tissue, perpetuating the organ alterations. Visceral fat, but also ectopic fat, either in the liver, muscle or heart, can increase the risk of developing insulin resistance, type 2 diabetes, and cardiovascular diseases. Being able to prevent and to target dysfunctional adipose tissue will avoid the progression towards the complications of obesity and other nutrition-related diseases. The aim of this review is to summarize some of the knowledge regarding the presence of adipose tissue in particular tissues (where it is not usually present), describing the composition of its adipogenic precursors, and the interactions responsible for the development of organ pathologies.

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Diabetes Mellitus Tipo 2 , Adipocitos/metabolismo , Adipogénesis , Adipoquinas/metabolismo , Tejido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Humanos

RESUMEN

Breast cancer represents the most commonly diagnosed cancer while neoadjuvant and adjuvant chemotherapies are extensively used in order to reduce tumor development and improve disease-free survival. However, chemotherapy also leads to severe off-target side-effects resulting, together with the tumor itself, in major skeletal muscle deconditioning. This review first focuses on recent advances in both macroscopic changes and cellular mechanisms implicated in skeletal muscle deconditioning of breast cancer patients, particularly as a consequence of the chemotherapy treatment. To date, only six clinical studies used muscle biopsies in breast cancer patients and highlighted several important aspects of muscle deconditioning such as a decrease in muscle fibers cross-sectional area, a dysregulation of protein turnover balance and mitochondrial alterations. However, in comparison with the knowledge accumulated through decades of intensive research with many different animal and human models of muscle atrophy, more studies are necessary to obtain a comprehensive understanding of the cellular processes implicated in breast cancer-mediated muscle deconditioning. This understanding is indeed essential to ultimately lead to the implementation of efficient preventive strategies such as exercise, nutrition or pharmacological treatments. We therefore also discuss potential mechanisms implicated in muscle deconditioning by drawing a parallel with other cancer cachexia models of muscle wasting, both at the pre-clinical and clinical levels.

RESUMEN

OBJECTIVES: To explore whether quadratic model will better estimate the relationship between aging and thigh tissue composition in a cohort that range in age from young to older adults. METHODS: 51 healthy subjects participated in this investigation. All subjects underwent CT imaging for the thigh. Cross-sectional area of the fat and muscular tissues in the thigh were quantified. Hierarchical regression models were created. Age was entered first into the models to estimate its linear relationship with the thigh tissues. Then the squared value of the age variable was entered second to identify whether a quadratic model would better estimate the relationship between the variables. RESULTS: The linear model was significant for thigh muscular tissue. Quadratic models were able to account for additional significant prediction of the cross-sectional area of thigh tissues. Muscular area decreased with aging until 60 years after that it didn't change. Fat areas increased with aging until 45-50 years and then it decreased. CONCLUSIONS: The cross-sectional area of different thigh tissues exhibit a curvilinear pattern with aging. Muscular tissue area may not change after 60 years; this could be explained by the reduction in fat that may infiltrate inside the muscles and offset the muscular reduction.

Asunto(s)

Composición Corporal , Muslo , Tejido Adiposo , Anciano , Envejecimiento , Estudios Transversales , Humanos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/metabolismo , Muslo/diagnóstico por imagen