Search Results (317)

Blood-based biomarkers allow monitoring of an individual’s health status and provide insights into metabolic and inflammatory processes in conditions like obesity, cardiovascular, and liver diseases. However, selecting suitable biomarkers and optimizing analytical assays presents challenges, is time-consuming and laborious. Moreover, knowledge of potential sex differences remains incomplete as research is often carried out in men. This study aims at enabling researchers to make informed choices on the type of biomarkers, analytical assays, and dilutions being used. More specifically, we analyzed plasma concentrations of >90 biomarkers using commonly available ELISA or electrochemiluminescence-based multiplex methods, comparing normal weight (BMI < 25; n = 40) with obese (BMI > 30; n = 40) adult blood donors of comparable age. To help choose optimal biomarker sets, we grouped frequently employed biomarkers into biological categories (e.g., adipokines, acute-phase proteins, complement factors, cytokines, myokines, iron metabolism, vascular inflammation), first comparing normal-weight with obese persons, and thereafter exploratively comparing women and men within each BMI group. Many biomarkers linked to chronic inflammation and dysmetabolism were elevated in persons with obesity, including several adipokines, interleukins, chemokines, acute-phase proteins, complement factors, and oxidized LDL. Further exploration suggests sex disparities in biomarker levels within both normal-weight and obese groups. This comprehensive dataset of biomarkers across diverse biological domains constitutes a reference resource that may provide valuable guidance for researchers in selecting appropriate biomarkers and analytical assays for own studies. Moreover, the dataset highlights the importance of taking possible sex differences into account. Full article

Background: Menopause increases the risk of cardiovascular diseases (CVD) accompanied by a decline in muscle function. Myokines, released by skeletal muscle, could play a significant role in cardiovascular health. Objectives and Methods: This study aimed to investigate the changes induced by a 16-week resistance training (RT) program and/or the docosahexaenoic acid (DHA)-rich n-3 PUFA supplementation on myokine and cytokine circulating levels and to study their associations with parameters of body composition, muscle function, and glucose and lipid serum markers in postmenopausal women with overweight/obesity. Results: At baseline, interleukin-6 (IL-6) levels were positively correlated with body fat and with tumor necrosis factor-alpha (TNF-α) levels and negatively associated with meterorin-like (METRNL) levels. Moreover, METRNL was inversely associated with insulin levels and with HOMA-IR. After the intervention, muscle quality improved with either treatment but more notably in response to RT. N-3 supplementation caused significant improvements in cardiometabolic health markers. TNF-α decreased in all experimental groups. Myostatin levels decreased in the RT and in the n-3 groups, and IL-6 increased in the n-3+RT group. Lastly, no interactions between treatments were observed. Conclusions: In postmenopausal women with overweight or obesity, RT could help improve skeletal muscle function, while DHA-rich n-3 supplementation might decrease CVD risk and might potentially improve muscle function. The modulation of myokine levels could be underlying some of the effects of DHA or RT; however, further research is necessary. Full article

Benign prostatic hyperplasia (BPH) is a multifactorial condition that is highly prevalent and affects aging males. It frequently results in lower urinary tract symptoms (LUTS) and a reduced quality of life. While hormonal dysregulation and chronic inflammation have long been implicated in BPH pathogenesis, recent evidence highlights the role of physical activity in modulating prostate health. In this narrative review, evidence from quantitative studies examining the effect of exercise on BPH risk and symptom severity was first synthesized. Collectively, these studies suggest that regular physical activity is associated with a lower incidence and reduced progression of BPH. The potential mechanisms through which exercise may exert protective effects on the prostate were then explored. These include modulation of sympathetic nervous system activity, alterations in hormonal profiles (e.g., testosterone and insulin), suppression of chronic inflammation and oxidative stress, and the promotion of autophagy within prostatic tissue. Central to these mechanisms is the role of myokines—signaling molecules secreted by skeletal muscle during exercise. Key myokines, such as irisin, interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and myostatin, are reviewed in the context of prostate health. These molecules regulate inflammatory pathways, metabolic processes, and tissue remodeling. For instance, exercise-induced reductions in myostatin are linked to improved insulin sensitivity and decreased fat accumulation, while elevated irisin and BDNF levels may exert anti-inflammatory and metabolic benefits relevant to BPH pathophysiology. Although direct causal evidence linking myokines to BPH is still emerging, their biological plausibility and observed systemic effects suggest a promising avenue for non-pharmacological intervention. Future research should focus on identifying the specific myokines involved, elucidating their molecular mechanisms within the prostate, and evaluating their therapeutic potential in clinical trials. Full article

Parathyroid hormone (PTH) has been studied to determine its broader role in musculoskeletal health, particularly its effects on skeletal muscle. Bone and muscle are inextricably linked via mechanical loading and biochemical signaling, with both processes playing important roles in muscular metabolism and function. Furthermore, the nervous system must maintain muscle mass and function, as neuromuscular transmission controls muscle contraction, protein synthesis, and energy metabolism. As a systemic endocrine regulator, PTH influences the physiology of skeletal muscle—both directly and through interactions with bone and the nervous system, modulating myokines, osteokines, and neuromuscular activity. The intricate relationships between PTH, muscle, bone, and nerves continue to be investigated due to their implications for aging, metabolic pathologies, and musculoskeletal disorders. Full article

Background/Objectives: Childhood cancer survivors (CCS) experience chronic health problems and significant metabolic burden. Timely identification of CCS at higher metabolic risk requires novel biomarkers. Irisin, a novel myokine/adipokine has been associated with metabolic, bone and reproductive diseases, but its role in the health of CCS is unknown. The aim of this study was to examine irisin concentrations in children and adolescent CCS (vs. controls) and their association with metabolic, bone and hormonal parameters. Methods: Children and adolescent CCS, aged 8–18 years, as well as healthy controls, underwent a detailed physical, body composition, biochemical, hormonal and serum irisin assessment at least 6 months post-treatment. Results: A total of 59 children and adolescents (36 CCS, 23 controls; mean age ± SD 12.8 ± 2.9 years; 10 prepubertal, 49 pubertal) participated in the study. Serum irisin concentrations (ng/mL) were significantly lower in CCS than controls [median (IQR) 6.54 (4.12) vs. 11.70 (8.75) ng/mL, respectively, p < 0.001]. In the total study sample, serum irisin was correlated negatively with LH (r_s = −0.314, p < 0.05), CRP (r_s = −0.366, p < 0.005), age (r_s = −0.323, p < 0.05) and positively with ALP (r_s = 0.328, p < 0.05). Serum irisin was also positively correlated with ApoB and Lpa (r_s = 0.410 and 0.421, respectively, p < 0.05) in CCS, and with PTH (r = 0.542, p < 0.005) in controls. Multivariate linear regression analysis indicated parathyroid hormone (PTH) as the only independent variable affecting irisin concentrations. Conclusions: Study results reinforce the irisin–PTH interplay hypothesis. Future studies are needed to clarify the potential role of irisin as a bone biomarker of CCS in childhood and adolescence. Full article

Previous research has demonstrated sex-specific differences in muscle cells regarding sex hormone release and steroidogenic enzyme expression after testosterone exposure. The present study aims to elucidate sex-related differences in intracellular processes involved in myogenesis and regeneration. Neonatal 46XX and 46XY human primary skeletal muscle cells were treated with increasing doses of testosterone (0.5, 2, 5, 10, 32, and 100 nM) for 24 h. The molecular pathways involved in muscle metabolism and growth, as well as the release of myokines involved in satellite cell activation, were analyzed using western blot, real-time PCR, and a Luminex assay. The unpaired Student’s t-test and one-way ANOVA for repeated measures were used to determine significant variations within and between groups. An increase in the expression and release of MYF6, IGF-I, IGF-II, and CXCL1, as well as a decrease in GM-CSF, IL-9, and IL-12, was observed in 46XX cells. Conversely, testosterone up-regulated GM-CSF and CXCL1 in 46XY cells but did not affect the release of the other myokines. Preferential activation of the MAPK pathway was observed in 46XX cells, while the PI3K/AKT pathway was preferentially activated in 46XY cells. In conclusion, our findings demonstrate differential responses to androgen exposure in 46XX and 46XY cells, resulting in the activation of muscle cell growth and energy metabolic pathways in a sex-specific manner. Full article

Skeletal muscle, traditionally recognized for its motor function, has emerged as a key endocrine organ involved in metabolic regulation and interorgan communication. This narrative review addresses the dual role of muscle as a target tissue for classical hormones—such as growth hormone (GH), insulin-like growth factor type 1 (IGF-1), thyroid hormones, and sex steroids—and as a source of myokines, bioactive peptides released in response to muscle contraction that exert autocrine, paracrine, and endocrine effects. Several relevant myokines are discussed, such as irisin and Metrnl-like myokines (Metrnl), which mediate exercise-associated metabolic benefits, including improved insulin sensitivity, induction of thermogenesis in adipose tissue, and immunometabolic modulations. It also examines how muscle endocrine dysfunction, caused by chronic inflammation, hormone resistance, or sedentary lifestyle, contributes to the development and progression of metabolic diseases such as obesity, type 2 diabetes, and sarcopenia, highlighting the importance of muscle mass in the prognosis of these pathologies. Finally, the therapeutic potential of interventions aimed at preserving or enhancing muscle function—through physical exercise, hormone therapy and anabolic agents—is highlighted, together with the growing research on myokines as biomarkers and pharmacological targets. This review expands the understanding of muscle in endocrinology, proposing an integrative approach that recognizes its central role in metabolic health and its potential to innovate the clinical management of endocrine–metabolic diseases. Full article

Blood flow restriction exercise (BFRE), which partially restricts arterial inflow and occludes venous outflow to the limbs, has gained attention for its potential to elevate serum brain-derived neurotrophic factor (BDNF), a key mediator in the muscle–brain crosstalk leading to improvement of neuroplasticity, neurogenesis, and cognitive health. In this systematic review of five studies, participants included healthy young adults, older adults, and individuals with clinical conditions. Most investigations found that BFRE increased serum BDNF, with responses comparable to those elicited by high-intensity exercise. Proposed mechanisms center on the metabolic demands of BFRE, which may increase lactate and thereby trigger BDNF release. However, two studies showed no significant changes, possibly due to short exercise duration, insufficient training intensity, or age-related reductions in BDNF responsiveness. The small sample sizes and varied protocols across studies limit definitive conclusions. Nonetheless, BFRE may provide a valuable alternative for populations who cannot tolerate high mechanical loads, and it shows promise for enhancing neurotrophic support and potentially improving brain health. Larger, well-controlled trials are warranted to refine BFRE protocols and better understand optimal strategies for increasing BDNF and supporting neuroplasticity. Full article

Exercise suppresses appetite in individuals with obesity irrespective of the type, duration, or intensity of the exercise. This effect is mediated through various physiological and biochemical mechanisms. Exercise influences appetite-regulatory hormones such as ghrelin and leptin, reducing hunger signals. Additionally, exercise generates metabolites and myokines, along with hepatokines, which modulate appetite suppression. Brain-derived neurotrophic factor (BDNF) is also implicated in modulating appetite. Changes in eating behaviors, gastric motility, and gastric emptying further contribute to a reduced appetite. Mental stress and body temperature alterations during exercise can also impact hunger levels. This review synthesizes current evidence and provides specific biochemical, metabolic and molecular mechanisms of how exercise and obesity affect appetite regulation. More specifically, it is extensively discussed the effect of exercise and obesity on: (1) endocrine mediators (hepatokines, metabolites, myokines, and neurotrophins); (2) physiological modulators (gastric emptying and body temperature); and (3) behavioral influences (eating patterns and visual food cues) in association with appetite regulation. Collectively, these factors highlight the complex interplay between physical activity and appetite regulation, offering insights into potential therapeutic strategies for managing obesity through exercise. Full article

Background/Objectives: During adolescence, the critical growth period, the antioxidant selenium (Se), either as sodium selenite or selenium nanoparticles (SeNPs), has shown contrasting effects on adipose tissue (AT) in rats, due to its role in insulin signaling. Since skeletal muscle (SKM) is also a key insulin-target tissue, this study aimed to assess whether a similar effect occurs in this tissue. Methods: Three groups of male adolescent rats (n = 18) were used: control (C), selenite supplemented (S), and SeNPs supplemented (NS). Low doses of Se were administered via drinking water in both supplemented groups. AT was utilized for transcriptomic analyses, while SKM was analyzed for oxidative balance, insulin-induced anabolic effects, and proteolysis. Myokine levels in serum were also determined. Results: SeNPs administration decreased SKM mass and protein content, increased serum creatinine, and decreased insulin levels, indicating impaired SKM development. Both supplemented groups upregulated genes related to creatine metabolism and muscle contraction. However, only the NS group showed upregulation of genes associated with glycogenolysis and glycolysis. Despite unchanged GPx1 expression, NS rats presented lower oxidation and insulin–pmTOR activation, and higher expression of proteins related to proteolysis (pAMPK, SIRT1, ULK1, FOXO3a, and MaFbx) and a myokine profile compatible to muscle atrophy, fatty acid oxidation, and impaired myoblast proliferation. Ultimately, the selenite group impaired SKM catabolism mainly by increasing insulin–pmTOR activation. Conclusions: Once again, the form of Se administration exerts opposing effects on metabolism tissues, suggests a potential therapeutic role for selenite in disorders that compromise muscle growth, such as muscular dystrophies, cachexia, or sarcopenia. Full article

Type 1 Diabetes Mellitus (T1D) is a disease characterized by the destruction of pancreatic beta cells. The subsequent loss of insulin production results in hyperglycemia, muscle wasting, and vascular dysfunction. Due to an inability to appropriately maintain glucose homeostasis, patients afflicted with T1D suffer from increased morbidity and early mortality. Skeletal muscle is the body’s largest metabolic reservoir, absorbing significant amounts of glucose from the bloodstream and physical exercise is known to improve and prevent the progression of pathological outcomes, but many T1D patients are unable to exercise at a level that conveys benefit. Thus, directly targeting muscle mass and function may prove beneficial for improving T1D patient outcomes, independent of exercise. A potent negative regulator of skeletal muscle has been identified as being upregulated in T1D patients, namely the myokine myostatin. Our hypothesis is that targeting myostatin (via genetic deletion) will prevent glucose dysfunction in a T1D model, preserve skeletal muscle function, and protect against vascular and renal dysfunction. Our methods utilized adult male mice with (WT) and without myostatin (Myo KO), in combination with the chemical induction of T1D (streptozotocin). Experimental outcomes included the assessment of glucose homeostasis (plasma glucose, HbA1c, IGTT), metabolism, muscle function (in vivo plantarflexion), and skeletal muscle vascular function (ex vivo pressure myography). Our results described systemic benefits from myostatin deletion in the T1D model, independent of insulin, including the following: inhibition of T1D-induced increases in plasma glucose, prevention of functional deficits in muscle performance, and preservation of fluid dynamics. Further, endothelial function was preserved with myostatin deletion. Taken together, these data inform upon the use of myostatin inhibition as a therapeutic target for effective treatment and management of the cardiometabolic and skeletal muscle dysfunction that occurs with T1D. Full article

Background: Recent studies indicate that in progressive multiple sclerosis (MS)—an inflammatory and degenerative disease of the central nervous system—the biological pathways associated with these effects remain poorly understood. Changes in body weight, whether presenting as overweight or underweight, as well as alterations in adipose and muscle tissue, together with chronic inflammation, may contribute to the disease and influence its course. Objective: This case–control study aimed to measure inflammatory markers and myokine levels (myostatin and irisin), brain-derived neurotrophic factor (BDNF), and IL-6 in the serum of patients with multiple sclerosis and healthy control and assess whether the myokines and cytokines are associated with nutritional status. Methods: The study included 92 MS patients and 75 healthy volunteers. Nutritional status was assessed using the NRS (Nutritional Risk Screening) 2002 and GLIM (Global Leadership Initiative on Malnutrition) criteria. The risks of malnutrition or malnutrition were diagnosed based on ESPEN recommendations. Body composition analysis was performed using the BIA method with the InBody 120 analyzer. Routine laboratory parameters (albumin, lipidogram) were measured. Myostatin, irisin, BDNF, IL-6, and hsCRP were measured using ELISA methods. Statistical analysis was conducted using Statistica 13.0 software. Comparisons between the two groups were conducted using Student’s t-test for normally distributed variables and the Mann–Whitney U test for non-normally distributed variables; the differences between groups were calculated using either ANOVA or the Kruskal–Wallis test. Post hoc analysis by the Bonferroni method was applied. Results: In the MS group, high risks of malnutrition (69.0%) and malnutrition (14.0%) were observed. A statistically significant correlation was found between malnutrition (GLIM) and s-albumin (R = 0.2; p < 0.05) and hsCRP (R = 0.23; p < 0.05). The MS patient group displayed significantly lower levels of irisin, higher levels of hsCRP, and lower s-albumin compared to healthy volunteers. Malnourished patients with MS exhibited significantly lower irisin levels, as well as higher hsCRP in comparison to MS patients who were at risk or well nourished. The levels of myostatin, BDNF, and IL6 did not differ depending on nutritional status. Irisin correlated with hsCRP (R Spearman = −0.5; p = 0.01). Conclusions: Our findings highlight the interplay between chronic inflammation, nutritional status, and myokines level in multiple sclerosis. Full article

The novel secreted protein Meteorin-β (Metrnβ) is a homologous protein of the neurotrophic regulator Meteorin, which is widely expressed in the skin, mucous membranes, and white adipose tissue upon stimulation by a variety of inflammatory mediators, including cytokines and chemokines, while, at the same time Metrnβ may also regulate the expression of these cytokines and chemokines. As a small secreted protein with low tissue specificity, Metrnβ plays vital roles in energy metabolism, insulin sensitivity regulation, neurodevelopment, white fat browning, and inflammatory response. Specifically, Metrnβ may act as an adipokine, myokine, neurotrophic factor, and cytokine, thereby being involved in the pathological and physiological processes of various human diseases, including metabolic, autoimmune and infectious/allergic diseases, and certain types of tumors. This review aims to systematically introduce the current research progress on Metrnβ, including its expression and distribution profiles, biological functions, and immunomodulatory roles in the process of human diseases. Additionally, we also discuss its potential as a biomarker, as well as a therapeutic/preventive agent for human diseases. Full article

Exercise potentially inhibits tumor growth. It remains unclear which processes mediate these effects. Alterations of cytokine concentration in serum can influence cancer cell growth and may cause cell growth inhibition. This pilot study examines whether exercise-induced conditioning in serum can directly affect tumor cells. It focuses on serum collected before and after acute endurance exercise and its impact in vitro. Participants underwent a 1 h endurance training on a cycle ergometer. Samples were collected before, after, and two hours post-exercise. MDA-MB-231 cells were incubated with serum, and cell vitality and proliferation were assessed. Cytokine arrays identified relevant cytokine concentration changes. After identifying CXCL9 as a possible contributor to inhibitory effects, we inhibited the CXCR3 pathway and reassessed vitality. Exercise-conditioned serum significantly reduced cell vitality and proliferation post-intervention and after resting. Cytokine arrays revealed changes in multiple concentrations, and the inhibition of CXCL9 resulted in growth inhibitory effects. Our findings suggest that serum conditioned by an endurance intervention causes changes in cancer cell growth. Based on our observations, the alterations in serum cause growth-inhibitory effects, possibly mediated through the CXCR3 axis. This study provides preliminary evidence supporting the role of exercise in modulating the cancer cell growth directly by changes in serum. Full article

Background/Objectives: Myokines can modulate organ function and metabolism, offering a protective profile against ICU complications beyond preventing local muscle wasting. This scoping review aims to explore and summarize the evidence regarding the secretion of myokines and their potential local or systemic effects in critically ill patients. Methods: A scoping review following Joana Briggs Institute recommendations was conducted. A systematic search of MEDLINE (Ovid), Embase (Ovid), CENTRAL, CINAHL (EBSCOhost), WoS, and Scopus was conducted from inception to February 2023. We included primary studies evaluating myokine secretion/concentration in critically ill adults undergoing physical rehabilitation interventions. Two independent reviewers performed study selection and data extraction. Results: Seventeen studies published between 2012 and 2023 were included. Most were randomized clinical trials (47%). Physical rehabilitation interventions included electrical muscle stimulation, as well as passive and active mobilization, delivered alone or combined, in single or daily sessions lasting 20–60 min. Twelve studies (70%) evaluated interleukin-6, while interleukin-10, tumour necrosis factor-α, Interleukin-8, and myostatin were also commonly studied. Thirteen studies (76%) reported changes in myokine secretion or gene expression, although no clear concentration change pattern emerged. Myokines involved in muscle protein synthesis and breakdown may protect against muscle waste and weakness. Conclusions: The study of myokine dynamics in critically ill patients highlights the systemic impact of physical rehabilitation. This emerging field has grown in interest over the past decade, offering significant research potential. However, challenges such as study design, small sample sizes, and variability in physical therapy protocols hinder a comprehensive understanding of myokine responses. Full article