Search Results (739)

Background: Proper nutrition plays a crucial role in post-kidney transplantation care, influencing graft function, body composition, and the risk of metabolic complications. Protein intake is of particular importance due to its role in preserving muscle mass and preventing protein energy wasting. Objective: This study aimed to assess dietary intake, with emphasis on protein consumption, and to analyze its associations with nutritional status, anthropometric indices, and metabolic complications in kidney transplant recipients. Materials and Methods: A cross-sectional study was conducted in 71 adult kidney transplant recipients. Dietary intake was assessed using a 24 h dietary recall and the FFQ-6 questionnaire. Anthropometric measurements were performed, and multiple indices of body composition and central obesity were calculated. Associations between dietary intake, anthropometric parameters, age, and kidney graft function were analyzed. Results: Mean BMI was within the upper normal range; however, a high prevalence of central adiposity was observed. Age was positively correlated with indices of visceral obesity (ABSI, AVI, WHtR, and CI). Protein intake was positively associated with calf circumference, indicating a relationship with muscle mass preservation. Dietary analysis revealed excessive sodium intake and insufficient intake of potassium, calcium, vitamin D, and unsaturated fatty acids. Post-transplant diabetes mellitus was present in 25.35% of participants. Conclusions: Kidney transplant recipients frequently present with unfavorable body composition and dietary imbalances that are not adequately reflected by BMI alone. Comprehensive nutritional assessment and individualized dietary counseling are important strategies that may help reduce the risk of metabolic complications and support long-term transplant outcomes. Full article

Severe burn injury results in systemic inflammation, edema, multiple organ disorder and muscle wasting. These events are provoked by the massive dysfunction of mitochondria not only in the burned skin but also in muscles and internal organs, which is induced by the release of damage-associated molecular patterns and catecholamines. Dysfunctional mitochondria are characterized by increased ROS production and the release of mitochondrial DNA, which lead to enhanced expression of proinflammatory cytokines. Mitochondria present a key target for treatment of severe burns, and various pharmacological approaches are being developed to protect normal mitochondrial functions after burn injury. Full article

Background: Muscle atrophy is a major feature of Limb Girdle Muscular Dystrophy R1 (LGMDR1) patients, but its underlying molecular mechanisms have not been fully explored. While the ubiquitin–proteasome system (UPS) is known to be involved in muscle protein degradation, inflammation commonly observed in LGMDR1 patients may further activate the UPS. This study aimed to explore the role of inflammation in the muscle atrophy of LGMDR1 patients. Methods: Muscle biopsies from six confirmed LGMDR1 patients (with CAPN3 variants and reduced calpain-3 protein expression) were analyzed for atrophy-related markers, MuRF1 and Atrogin-1, using qRT-PCR and Western blotting. The expression of cytokines, TNF-α, IL-1β, and IL-6 was analyzed by qRT-PCR from muscle biopsies and by ELISA from serum samples. The NFκB, FOXO1, and FOXO3 gene expression was analyzed using qRT-PCR and Western blotting from muscle biopsies. Results: Elevated TNF-α levels were associated with increased UPS activity, reflected by upregulated NFκB, FOXO1, MuRF1, and Atrogin-1 expression in LGMDR1. Conclusion: Our findings indicate that increased TNF-α expression is associated with muscle wasting in LGMDR1 patients by targeting UPS pathway mediators that activate ubiquitin ligases—MuRF1 and Atrogin-1. These findings suggest that targeting TNF-α signaling and its downstream factors may help develop therapeutic interventions to prevent muscle atrophy in LGMDR1 patients. Full article

Background/Objectives: Obesity has a huge impact on global healthcare and economy. Consequently, the pharmaceutical industry has recently introduced novel anti-obesity drugs such as semaglutide and tirzepatide, which can yield remarkable weight reduction in patients, while also having significant cardiovascular benefits. Methods: Other weight-lowering medications are currently under investigation, and this narrative review provides an overview of the main novel drugs that are being tested. Results: These novel agents have different mechanisms of action, e.g., calorie intake reduction, increase in basal metabolism, and increase in muscle mass. Conclusions: In the future, obesity treatment is likely to become increasingly personalized, and further cardiovascular benefits could be expected. The combined use of different molecules could minimize their side effects, for instance, by minimizing muscle wasting observed during glucagon-like peptide 1 receptor agonists (GLP1-RAs) therapy. In our opinion, these highly effective drugs could represent a valuable addition to healthy lifestyle, as the evidence linking increases in muscle mass and basal metabolic rate to improved cardiovascular health is strongest when these changes are achieved through diet and regular physical activity. Full article

Purpose: Cachexia, characterized by involuntary weight loss, muscle wasting, and metabolic dysfunction, is prevalent in advanced cancer and chronic illnesses. Despite its impact, outpatient treatment models in the U.S. remain limited and unstandardized. Here, we aim to describe the structure, implementation, patient characteristics, and real-world clinical trajectories of a multidisciplinary clinic for cancer cache as well as other forms of unintentional weight loss clinic within an academic endocrinology practice. Methods: We conducted a retrospective observational cohort study of 103 patients referred to a single-center unintentional weight loss clinic over five years. Patients received comprehensive assessments (weight trajectory, nutrition status, 5× sit-to-stand test, handgrip strength) and personalized interventions including nutrition counseling, resistance training, and pharmacologic therapies. Results: Among 103 patients (median age 69.7 years; 53% male), 64% had cancer, while 36% were referred for non-malignant causes of weight loss or cachexia. Reduced appetite or food intake was reported in 43%, and functional impairment was common, with low handgrip strength in 47% and impaired 5× sit-to-stand performance in 79% of assessed patients. Systemic abnormalities were frequent, including elevated hs-CRP (57%), elevated neutrophil-to-lymphocyte ratio (43%), and hypoalbuminemia (26%). Among patients with available paired follow-up data, the median rate of weight change shifted from −0.5 kg/month prior to enrollment to 0.0 kg/month three months after the initial visit (p < 0.0001). Five-times sit-to-stand performance improved modestly at three months (p = 0.042), while handgrip strength was unchanged. Half of patients that engaged with the clinic returned for at least follow-up, but there was no identifiable difference between the population of patients that returned versus those that did not. Conclusions: A structured, multidisciplinary unintentional weight loss clinic in an endocrinology setting was associated with stabilization of weight and modest changes in physical function in this single-center cohort among patients who engaged in follow-up. These findings highlight the successful implementation of integrated outpatient care models and provide practice-based context for future interventions and therapeutic evaluations. Full article

Chronic obstructive pulmonary disease, interstitial lung disease, and post-lung trans-plantation are often accompanied by skeletal muscle dysfunction that worsens the quality of life. Such physiological changes are driven by physical inactivity, systemic inflammation, oxidative stress, anabolic and hormonal resistance, and medication effects. Structural changes include impaired capillarization, fiber-type shifts (slow-to-fast in limb muscle and fast-to-slow in respiratory muscles), mitochondrial dysfunction, reduced oxidative capacity, and early lactate accumulation. Electromyography and dynamometry, both isokinetic and isometric, quantify neuromuscular drive through measuring strength, power, and endurance and are associated with functional outcomes (6-min walk, sit-to-stand, stair climbing tests). Pulmonary rehabilitation (PR) improves neuromuscular efficiency, dyspnea, exercise tolerance, and quality of life by combining resistance, endurance, and eccentric training. The effects of PR generally plateau at three months, emphasizing the need for maintenance and the personalization of rehabilitation plans. While nutritional optimization is important, supplements have shown little benefit. Future priorities include defining EMG/dynamometry thresholds to allow standardized routine testing for comparable benchmarks and more precise PR protocols. Future research targeting mitochondrial remodeling, inflammatory signaling, and anabolic resistance offer potential pathways for preventing and reversing muscle wasting. Full article

Sarcopenia, characterized by the progressive loss of skeletal muscle mass, strength, and function, represents a major public health challenge in aging populations. This condition affects approximately 10–16% of community-dwelling older adults and is associated with increased risks of falls, frailty, functional decline, and mortality. The pathogenesis of sarcopenia involves chronic low-grade inflammation (inflammaging), oxidative stress, mitochondrial dysfunction, and anabolic resistance. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have emerged as promising nutritional interventions due to their anti-inflammatory properties and potential anabolic effects on skeletal muscle. This comprehensive review evaluates the current evidence on omega-3 PUFA supplementation for the attenuation and management of sarcopenia. Mechanistically, omega-3 PUFAs appear to enhance muscle protein synthesis through activation of the mTOR-p70S6K signaling pathway, reduce inflammation via specialized pro-resolving mediators (SPMs), improve mitochondrial bioenergetics, and attenuate muscle disuse atrophy. Clinical trials demonstrate that omega-3 supplementation, particularly at doses exceeding 2 g/day of combined EPA and DHA, can increase thigh muscle volume, handgrip strength, and one-repetition maximum strength in older adults. When combined with resistance exercise training, the benefits appear more pronounced, especially in women. However, heterogeneity in study designs, intervention durations, dosages, and outcome measures has produced some conflicting results. Large-scale trials, such as the MAPT study, have shown null findings for long-term supplementation alone, suggesting that omega-3s may be most effective as part of multimodal interventions. The evidence also supports benefits in clinical populations at risk for muscle wasting, including cancer patients experiencing cachexia and individuals with neuromuscular disorders. Future research should focus on identifying optimal dosing strategies, understanding sex-specific responses, and elucidating the mechanisms underlying the synergistic effects of omega-3s with exercise. Overall, omega-3 PUFA supplementation represents a safe, accessible, and potentially effective nutritional strategy for attenuating muscle decline in aging and clinical populations, though its benefits appear most pronounced when combined with resistance exercise as part of a multimodal approach. Full article

Pulmonary arterial hypertension (PAH) has traditionally been viewed as a vasculocentric disorder, with current therapies failing to reverse vascular remodeling or address pervasive systemic metabolic abnormalities. This review synthesizes emerging evidence to propose a paradigm shift, conceptualizing PAH as a systemic metabolic–immunological network disease. It examines how metabolic dysfunction in peripheral organs (adipose tissue, liver, skeletal muscle) and immunometabolic reprogramming of immune cells (e.g., macrophages, lymphocytes) synergistically drive pathology. These components engage in dynamic crosstalk via circulating mediators (metabolites, adipokines, cytokines), creating a self-amplifying loop that fuel pulmonary vascular inflammation and remodeling. Key mechanisms explored include adipose tissue endocrine dysfunction (contributing to the obesity paradox), hepatic insulin resistance and bile acid signaling, skeletal muscle energy crisis and wasting, and the pivotal roles of macrophage glycolytic polarization and T-cell subset imbalance. Insulin resistance/hyperglycemia emerges as a central hub linking metabolic and immune dysregulation. The review concludes that future therapeutic strategies must move beyond vasodilation to target this systemic network, discussing the potential of repurposed metabolic agents, direct immunometabolic modulators, and integrated lifestyle interventions to disrupt disease progression. Full article

Maintenance of skeletal muscle mass is essential for mobility, metabolic homeostasis, and clinical outcomes across a wide spectrum of physiological and pathological conditions. While muscle atrophy and hypertrophy have traditionally been interpreted through upstream anabolic–catabolic signaling and proteolytic pathways, accumulating evidence indicates that ribosome biogenesis and translational control represent rate-limiting determinants of muscle plasticity. However, this regulatory layer remains insufficiently integrated into current models of muscle adaptation and disease. In this review, we synthesize recent advances in ribosomal RNA transcription, ribosomal protein dynamics, and translational regulation in skeletal muscle, with particular emphasis on signaling networks governed by mTORC1, c-Myc, AMPK, and FOXO. We highlight ribosome biogenesis as a central hub linking mechanical loading, nutrient availability, inflammatory stress, and metabolic status to protein synthesis capacity. Evidence from human and animal studies demonstrates that impaired ribosome production and translational efficiency precede and predict muscle atrophy in disuse, aging, cancer cachexia, and chronic disease, whereas ribosome expansion is a prerequisite for sustained hypertrophy. Beyond quantitative regulation, we discuss the emerging concept of ribosome heterogeneity as a qualitative layer of translational control that may enable selective mRNA translation during muscle growth, stress adaptation, and degeneration. We further examine ribosome–mitochondria crosstalk as a critical but underexplored mechanism coordinating anabolic capacity with cellular energetics. Finally, we outline therapeutic implications, highlighting exercise, nutritional strategies, and indirect pharmacological interventions that preserve ribosomal competence, and propose ribosome-based biomarkers as promising tools for precision management of muscle-wasting disorders. Collectively, this review positions ribosome biology as a translationally relevant framework bridging molecular mechanisms with therapeutic perspectives in skeletal muscle atrophy and hypertrophy. Full article

Cancer cachexia, characterized by severe body weight loss, negatively affects patient quality of life and survival. Although moderate exercise benefits healthy and chronically ill individuals, and the effect of exercise in cachexia generally appears beneficial, conflicting results have been reported in cancer-associated cachexia. This study examined the effects of moderate aerobic exercise in a rat cancer model, focusing on molecular crosstalk among tumors, serum, and skeletal muscle. Male Sprague-Dawley rats were divided into Non-Cancer, Cancer, and Cancer + Exercise (Ex) groups. Cancer was induced with an intraperitoneal injection of 7,12-dimethylbenz[a]anthracene (DMBA), and the Cancer + Ex group completed an eight-week treadmill regimen. Tibialis anterior muscle, serum, and tumor tissues were analyzed by RNA sequencing. DMBA injection produced sarcoma-like tumors, reduced body weight, elevated inflammatory mediators, and activated muscle atrophy genes (Fbxo32). Exercise led to progressive intolerance, further weight loss, lower muscle mass, and larger tumors. Transcriptomic profiling revealed exacerbated cachexia signatures and suppressed energy metabolism genes in exercised cancer rats. Bioinformatic analysis of serum proteins and tissue transcriptomes identified enhanced chemokine-receptor signaling, including pro-tumorigenic (CXCL6_CXCR2) and pro-cachexia (CCL19_CXCR3, CCL5_CCR3, CXCL11_CXCR3) interactions. These findings suggest that in a pro-inflammatory cancer context, late-onset moderate exercise may worsen cachexia and stimulate tumor progression. Thus, exercise protocols should be cautiously tailored in cancer settings. Full article

Background/Objectives: Intensive care unit-acquired weakness (ICUAW) is a frequent complication characterized by symmetrical and proximal limb muscle weakness. Its diagnosis is primarily based on clinical symptoms; however, ICUAW assessment can often be uncertain. Blood biomarkers have not yet been widely investigated for this purpose. Serum gelsolin (GSN) is synthesized by skeletal muscle cells. It plays a crucial role in binding extracellular actin filaments and pro-inflammatory cytokines. In sepsis-associated ICUAW, GSN levels might massively decrease due to their buffering activity and muscle wasting. We elucidated the predictive capacity of GSN regarding ICUAW and its additional diagnostic/prognostic potential in sepsis compared to classical parameters. Methods: We recruited septic and non-septic ICU patients for our follow-up study. Patients were retrospectively categorized into ICUAW positive (n = 26) and negative (n = 47) groups based on their clinical characteristics. Sera were collected on the 1st, 2nd and 3rd days of ICU stay. Ambulatory patients (n = 34) served as controls. GSN levels were measured by our previously developed automated immunoturbidimetric assay. Clinical and laboratory parameters were collected from our hospital information system. Results: Admission GSN levels were significantly reduced in ICU patients compared to controls (median: 11.60 vs. 75.99 mg/L). ICUAW positive patients had significantly lower admission GSN levels than ICUAW negative patients (median: 8.10 vs. 14.30 mg/L), and a similar tendency was observed during follow-up. GSN showed predictive capacity regarding ICUAW (ROC AUC: 0.711, p < 0.01), especially when combined with albumin (ROC AUC: 0.750, p < 0.01). The combination of admission GSN, albumin, and procalcitonin demonstrated significant diagnostic performance (ROC AUC: 0.803) regarding the requirement for invasive ventilation, and GSN had prognostic value for 28-day mortality as well. Conclusions: GSN might serve as an intriguing marker in the prediction of ICUAW, especially when combined with albumin. The parallel decline of GSN and albumin could reflect the combined effects of systemic inflammation and muscle wasting seen in ICUAW. Full article

Liver cirrhosis represents the end stage of chronic liver disease arising from diverse etiologies and is characterized by persistent hepatic injury, architectural distortion, extensive fibrosis, and nodular regeneration. While decompensated cirrhosis is commonly associated with overt, life-threatening complications such as hepatic encephalopathy, hepatorenal syndrome and gastrointestinal bleeding, less apparent manifestations—including sarcopenia and metabolic disturbances—have emerged as major determinants of prognosis. Sarcopenia, defined by the progressive loss of skeletal muscle mass and function, is highly prevalent in cirrhotic patients and is closely linked to frailty, increased morbidity, mortality, and adverse liver transplantation outcomes. Increasing data support the role of gastrointestinal dysfunction in the pathogenesis of sarcopenia in liver cirrhosis. In chronic liver disease, intestinal dysfunction is exacerbated by portal hypertension, which promotes increased intestinal permeability and bacterial translocation. Furthermore, gut dysbiosis, a key feature of advanced liver disease, contributes to impaired digestion, malabsorption of macro- and micronutrients, increased intestinal permeability, malnutrition and systemic inflammation. These alterations promote negative energy balance, reduce muscle protein synthesis and enhance muscle catabolism, thereby accelerating muscle wasting. Despite increasing recognition of the individual roles of gut dysbiosis, malabsorption, and sarcopenia in cirrhosis, their complex interrelationship has not been comprehensively addressed. This narrative review synthesizes current evidence on the interplay between gut dysbiosis, malabsorption and sarcopenia in patients with liver cirrhosis. We discuss underlying pathophysiological mechanisms, clinical implications and potential therapeutic strategies, while highlighting existing knowledge gaps and future research directions. Improved understanding of the gut-liver-muscle axis may offer novel opportunities for early intervention and optimization of outcomes in this high-risk patient population. Full article

Background/Objectives: Cancer cachexia involves progressive skeletal muscle and adipose tissue loss, which is further aggravated by cisplatin chemotherapy via increased systemic inflammation, tissue catabolism, and renal toxicity. The present study aimed to evaluate whether a combination of amaranth protein hydrolysate and Agastache rugosa extract (AKE) could attenuate cisplatin-associated cachexia and nephrotoxicity in CT26 tumor-bearing mice. Methods: Cancer cachexia was induced by subcutaneous CT26 cell inoculation in 6-week-old male BALB/c mice, followed by a 7-day tumor establishment period. Cisplatin was then administered intraperitoneally, and AKE (125 or 250 mg/kg/day) was given daily by oral gavage for 14 days. Results: AKE administration significantly alleviated cisplatin-induced body weight loss and systemic inflammation, accompanied by preservation of skeletal muscle and adipose tissue mass, as well as increased myofiber cross-sectional area and adipocyte size. AKE markedly reduced serum inflammatory cytokines, blood urea nitrogen, and creatinine levels, indicating protection against cisplatin-induced renal injury. Mechanistically, AKE suppressed renal apoptosis through inhibition of mitogen-activated protein kinase signaling. In skeletal muscle, AKE attenuated muscle atrophy by modulating protein turnover pathways, including downregulation of muscle-specific ubiquitin ligases and restoration of Akt/mTOR and FoxO3a signaling. Furthermore, AKE mitigated adipose tissue wasting by suppressing AMP-activated protein kinase-dependent browning and restoring adipogenic signaling involved in lipid storage and differentiation. Conclusions: These findings demonstrate that AKE confers comprehensive protection against cisplatin-induced cachexia and nephrotoxicity by coordinately preserving muscle and adipose tissue and attenuating renal injury, suggesting its potential as a functional nutritional strategy to alleviate chemotherapy-associated tissue wasting. Full article

Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive skeletal muscle and adipose tissue loss, systemic inflammation, and poor clinical outcomes, and represents a major unmet clinical need in gastric cancer. Growth Differentiation Factor 15 (GDF15) is a key mediator of cachexia-associated anorexia and tissue wasting; however, the upstream mechanisms regulating its expression in gastric cancer remain poorly defined. Leukemia Inhibitory Factor (LIF), a pleiotropic cytokine implicated in tumor progression and metabolic dysregulation, has emerged as a potential regulator of cachexia-related pathways. Here, we investigated the association between LIF in regulating GDF15 expression and its relationship with metabolic, inflammatory, and body composition alterations in gastric cancer. Transcriptomic profiling of paired neoplastic and non-neoplastic gastric mucosa from 61 gastric cancer patients revealed a significant upregulation of both LIF and GDF15 in tumor tissue, with a strong positive correlation between their expression levels. High GDF15 expression was associated with reduced overall survival, a finding validated in independent TCGA-STAD and ACRG cohorts. Intratumoral bile acid profiling uncovered a marked enrichment of primary bile acids and a depletion of secondary bile acids, resulting in reduced levels of bile acids with endogenous LIF receptor (LIFR) antagonist activity; elevated primary, LIFR non-antagonist bile acids were associated with worse survival outcomes. Clinically, increased LIF and GDF15 expression correlated with weight loss, heightened inflammatory burden, reduced serum protein and albumin levels, and impaired body composition in a sub-cohort of 19 patients. Notably, LIF expression showed a significant inverse association with both lumbar skeletal muscle index (L3SMI) and subcutaneous adipose tissue index (SATI). Mechanistically, experimental models demonstrated that LIF enhances proliferative activity in gastric cancer spheroids and exerts paracrine effects that impair myogenic differentiation and suppress hepatic metabolic gene expression. Collectively, these findings identify the LIF/GDF15 axis as a central driver of cancer-associated cachexia in gastric cancer and highlight LIF signaling as a potential therapeutic target. Full article

Background/Objectives: Muscle wasting is often observed in the acute phase after spinal cord injury (SCI). We aim to investigate the factors determining rectus femoris muscle thickness and echo intensity on discharge for patients who had acute incomplete spinal cord injury undergoing inpatient rehabilitation. Methods: This is a prospective exploratory observational cohort study, conducted in a standalone inpatient multi-specialty tertiary rehabilitation center in Singapore. Forty-five patients with incomplete SCI, defined as American Spinal Injury Association Impairment Scale (AIS) B–D were recruited from January 2020 to October 2021. Variables including clinico-demographic data, lower limb spasticity, Lower Extremity Muscle Score (LEMS), Functional Independence Measure (FIM) motor score on admission were collected. Muscle ultrasound of the rectus femoris thickness and echo intensity were obtained at 6 weeks after acute SCI via standardized protocols. Stepwise multiple regression analyses were performed to identify the factors that were significant for rectus femoris muscle thickness and echo intensity on discharge. Results: The mean age of participants was 59.6 ± 16.6 years, with patients having AIS of B (11.1%), C (28.9%) or D (60.0%). Rectus femoris muscle thickness on discharge had a significant association with body mass index (B = 4.62; CI = 1.77, 7.47; p = 0.002) and onset of mobilization (B = −4.97; CI = −9.46, −0.484; p = 0.031). The significant variables associated with rectus femoris echo intensity on discharge were age (B = 0.546; CI = 0.126, 0.967; p = 0.012) and onset of mobilization (B = 2.49; CI = 0.439, 4.53; p = 0.019). Conclusions: Our findings suggest that age, body mass index and a delayed onset of mobilization may have significant impact on muscle ultrasound parameters. Patients with incomplete SCI may benefit from early mobilization and nutritional assessment for improved muscle strength and function. Full article