Gestational diabetes mellitus (GDM) affects 9-25% of pregnancies. Undiagnosed or poorly managed GDM is associated with both short- and long-term complications in the fetus and mother. The pathogenesis of GDM is complex and has not yet been fully elucidated. Several biomarkers found in maternal serum have the potential for the early diagnosis of GDM. The aim of this narrative review was to explore novel biomarkers that have not been comprehensively described in previous reviews. We believe these biomarkers may allow for the detection of GDM in the early stages of pregnancy, enabling timely proper treatment and potentially preventing complications for both the mother and the fetus.

This research aims to reduce white striping muscle defects induced by vascular inflammation and hypoxia using the anti-inflammatory, antiplatelet and anti-atherothrombotic properties of acetylsalicylic acid (ASA). To this end, the effects of different doses (0.3, 0.6, 1, 3 and 6 g L-1) of ASA added to drinking water at 24-48 days on growth performance, carcass traits, footpad dermatitis, white striping and breast meat quality parameters were investigated.

The results indicate that 0.3, 1, 3 g L-1 and especially 0.6 g L-1 ASA treatment significantly improved growth performance and meat quality parameters. Also, doses of 0.3, 6 g L-1 and especially 0.6 g L-1 of ASA treatment reduced the incidence of white stripe muscle defects.

Consequently, 0.6 g L-1 ASA treatment reduced macrophage infiltrations and myodegeneration caused by growth rate. In addition, this dose increased vascular endothelial growth factor and decreased irisin level in breast muscle. The study also shows that high doses of ASA treatment (3 and 6 g L-1) may make footpad dermatitis more common. This may be due to the fact that ASA can cause side effects such as gizzard ulcers and kidney damage in broiler chickens. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Irisin is a newly identified hormone secreted mainly by skeletal muscles. It has different effects on the cardiovascular system and blood vessels. The present study investigated the possible effects of irisin on the microscopic structure of the perivascular adipose tissue in the rat thoracic aorta.

Twenty rats were randomly divided into two groups: a non-injected control group (n=4) and four injected experimental groups (each n=4). The experimental rats were injected intraperitoneally with one of the following concentrations of irisin; 250, 500, 1000, and 2000ng/mL, twice a week for 4 weeks. After that, all experimental rats' descending thoracic aortas were removed, and imaging was performed. ANOVA and Bonferroni's Multiple Comparison Test were used to achieve statistical comparisons.

A trend of a dose-dependent increase in the number of brown adipocytes in all irisin-injected groups reached statistical significance at a dose of 2000ng/mL, compared to that of the control group (from 7.9±1 control to 67±6.1 in 2000ng/mL of irisin). A dose-dependent decrease in the number of white adipocytes compared to that of the control group (from 40±4.8 control to 3±0.9 in 2000ng/mL of irisin).

The present study has for the first time demonstrated that irisin has significantly increased the number of brown adipocytes and decreased the number of white adipocytes in the perivascular adipose tissue in rat thoracic aorta.

Sarcopenia, characterized by progressive muscle mass and strength decline, poses a significant health challenge among older adults, especially those with chronic diseases. Our study aims to evaluate the combined diagnostic potential of irisin, 25(OH)D3, and albumin for sarcopenia in older patients with chronic conditions.

A cohort of 393 older patients with chronic diseases, including 117 diagnosed with sarcopenia were included. Fasting blood samples were collected, and serum biomarkers (25(OH)D3, albumin, and irisin) were measured using automated biochemical analyzers and enzyme-linked immunosorbent assay to evaluate nutritional and muscle-related parameters.

The prevalence of sarcopenia was higher among patients aged 80 or older compared to younger age groups in our study population. Strong associations were observed between sarcopenia and osteoporosis, tumors, and risk of malnutrition. Serum irisin, 25(OH)D3, and albumin levels were significantly lower in sarcopenic patients. Individual biomarkers displayed diagnostic potential, and a combined biomarker test showed superior accuracy. Multivariate logistic regression identified age, osteoporosis, malnutrition, and fatigue as independent risk factors, while higher serum biomarker levels correlated with reduced sarcopenia risk. Positive correlations were observed between serum biomarkers and sarcopenia severity indicators.

This study highlights the potential of irisin, 25(OH)D3, and albumin as diagnostic and prognostic tools for sarcopenia in older patients with chronic diseases, contributing to early detection and intervention strategies to enhance their quality of life.

Abnormal lipid droplet (LD) dynamics in oral squamous cell carcinoma (OSCC) indicate lipid metabolism alterations that facilitate malignancy progression. However, the specific mechanisms by which disruptions in lipid homeostasis affect malignancy processes remain poorly understood. This study investigated the role of LD-associated protein Caveolin2 (CAV2) in OSCC lipid homeostasis and progression.

The clinical relevance of CAV2 in OSCC was assessed through transcriptomics, single-cell sequencing, and functional validation in OSCC cells. CAV2 knockdown via shRNA was used to analyze its effects on growth, apoptosis, lipid homeostasis, and mitochondrial function. RNA sequencing, lipidomics, and molecular docking elucidated mechanisms of lipid metabolic disruption. Lipolysis was evaluated via glycerol release, lipidomics, and expression of related genes and proteins. Seahorse assays were used to evaluate mitochondrial dysfunction by analyzing mitochondrial respiration, while additional experiments assessed ROS levels, MMP, morphology, mass, and organelle interactions. In vivo, studies examined tumor progression in nude mice implanted with CAV2-knockdown OSCC cells. The regulatory role of PPARγ on CAV2 was explored through bioinformatics, correlation analysis, and dual-luciferase assays. Coimmunoprecipitation assessed CAV2 and NCOR1 binding with PPARγ, while the PPARγ inverse agonist T0070907 was used to enhance NCOR1-mediated repression of CAV2.

CAV2 was upregulated in OSCC and correlated with poor clinical outcomes. CAV2 knockdown increased apoptosis, reduced proliferation, and disrupted lipid homeostasis, elevating polyunsaturated fatty acids (PUFAs). Regulatory networks responsible for PUFA accumulation were mapped in CAV2-knockdown OSCC cells, from upstream regulators to downstream effects. Furthermore, lipolysis and mitochondrial dysfunction were also enhanced following CAV2 silencing. In vivo, CAV2 knockdown suppressed OSCC progression. Mechanistically, PPARγ regulated CAV2 transcription via NCOR1, but OSCC cells disrupted this repression. The PPARγ inverse agonist T0070907 restored NCOR1-mediated repression, synergistically enhancing the effects of CAV2 knockdown on apoptosis, lipolysis, and mitochondrial dysfunction.

Alteration of CAV2 disrupted lipid homeostasis and inhibited OSCC progression by affecting key processes, including apoptosis, lipolysis, and mitochondrial dysfunction. The disruption was driven by the dysregulation of the PPARγ/NCOR1 axis, highlighting the potential of targeting CAV2 and its interaction with PPARγ as a therapeutic strategy for OSCC.

Cognitive impairment is highly prevalent among individuals with chronic kidney disease (CKD). Despite its high prevalence, the contributing factors and mechanisms underlying brain-kidney dysfunction in CKD remain poorly understood. However, advances in neuroscience, including novel imaging techniques and cognitive assessment methods, have begun to clarify this complex relationship. Several factors contribute directly to cognitive decline in people with CKD, including accumulation of uraemic toxins, microvascular damage, malnutrition, chronic inflammation and disruptions in key neuroprotective pathways, such as those involving Klotho and the glymphatic system. These factors are also linked to the accelerated ageing observed in people with CKD, a key contributor to cognitive decline. However, most studies on cognition in people with CKD have been cross-sectional and associative, offering limited insight into causation. Research advances, such as studies on the effect of uraemic toxins on the blood-brain barrier and the role of the endothelial glycocalyx in vascular damage, offer promising new directions. Emerging data from longitudinal cohort studies are also enhancing our understanding of these processes, with potential implications for both the treatment of CKD-related cognitive decline and the broader issue of cognitive dysfunction in ageing populations. Here, we examine key mechanisms linking CKD to cognitive decline and consider potential therapeutic interventions.

Relative muscle strength (RMS) serves as a valuable indicator of skeletal muscle function. As the body ages, skeletal muscle function declines gradually, leading to a range of adverse effects. Cardiometabolic multimorbidity (CMM) is a prevalent co-morbidity in middle-aged and elderly populations. However, there are few studies to investigate the association between RMS and CMM.

This study adopted a cross-sectional design, including participants from the China Health and Retirement Longitudinal Study (CHARLS) of 2011. Appendicular skeletal muscle mass (ASM) was estimated using previously validated anthropometric equations. RMS was defined as the ratio of maximum hand grip strength (HGS) to ASM. CMM was characterized by the presence of at least two cardiometabolic disorders (cardiopathy, stroke, and diabetes), as assessed through self-reported physician diagnoses. The relationship between RMS and CMM was evaluated through multifactor logistic regression analysis.

A total of 9,200 participants with a mean age of 59.49 years were included in this study. Among them, 6,844 (74.4%) had no cardiometabolic disease (CMD), 2,052 (22.3%) had a single CMD, and 304 (3.3%) had cardiometabolic multimorbidity (CMM). Multifactor logistic regression was used to evaluate the relationship between them. In the initial model, there was a negative correlation between RMS and CMM. After adjusting for confounders, this association remained statistically significant. Specifically, for each additional unit increase in RMS, the risk of CMM was reduced by 40% (OR: 0.60, 95%CI: (0.45, 0.78)). Additionally, the highest RMS value group had a lower risk of CMM compared to the lowest value group (OR: 0.46, 95%CI: (0.31, 0.67)). As indicated by the restricted cubic spline plots, there was an L-shape correlation between RMS and CMM (P for nonlinear = 0.003).

The RMS, calculated based on HGS and ASM, was a potential indicator of CMM in middle-aged and elderly adults in China.

The global increase in life expectancy has led to a concomitant rise in diagnoses of sarcopenia. At the same time, the epidemic levels of obesity have given rise to the emergence of a complex condition known as sarcopenic obesity. Characterized by the simultaneous presence of loss of muscle mass and strength along with obesity or excess body fat, sarcopenic obesity represents a concerning health condition. Contrary to prevailing assumptions, sarcopenic obesity is not exclusive to older adults, as it may also manifest in individuals with obesity and chronic diseases and in those who undergo rapid weight loss. This juxtaposition of fat accumulation and muscle depletion epitomizes a harmful combination, especially in healthy adults. A precise definition of sarcopenic obesity and an understanding of how different body composition components affect functional parameters, comorbidities, and mortality rates are crucial for grasping the full extent and significance of this condition. Despite its multifaceted nature, sarcopenic obesity is often undiagnosed and undertreated, posing a considerable challenge to healthcare systems worldwide. In this review, we explore the intricate interplay of factors contributing to the development and consequences of sarcopenic obesity and discuss newly proposed diagnostic guidelines aimed at improved screening. Enhancing awareness and understanding of sarcopenic obesity is imperative for addressing its growing prevalence and mitigating its adverse health effects.

Irisin, a myokine released during physical exercise, has emerged as a key mediator of muscle health and metabolic regulation. This review synthesizes current evidence on how aerobic exercise stimulates irisin release and its subsequent effects, including enhanced muscle mass, strength, and recovery. Additionally, irisin promotes the browning of white adipose tissue, improving fat metabolism and glucose regulation. These adaptations position irisin as a promising therapeutic target for preventing metabolic disorders and optimizing exercise protocols. By exploring human studies and mechanistic insights, this review underscores irisin's potential to address global health challenges, such as obesity and type 2 diabetes, while advancing strategies for personalized exercise interventions.

Fibronectin type-III domain containing protein-5 (FNDC5), predominantly expressed in skeletal muscles, encodes FNDC5 transmembrane-protein. A segment of this protein is cleaved and secreted into blood as irisin, which promotes browning of white adipose tissue, leading to energy expenditure. It functions synergistically with fibroblast growth factor-21 (FGF21). Irisin is considered as a potential target for treating obesity-related disorders. Likewise, FNDC5 variations can contribute to development of such disorders. This study aimed to identify putative non-synonymous single nucleotide polymorphisms (nsSNPs) of human FNDC5, potentially impacting FNDC5-FGF21 interaction. Sequence and structure based computational tools were used to identify nsSNPs of FNDC5, which revealed eight nsSNPs as being most deleterious (N39K, R78H, R209H, T124I, L150P, L156V, V83M, and T86I). Molecular-docking was performed to analyze the impact of FNDC5 mutations on wild-type and mutant FNDC5-FGF21 complexes, revealing that T124I (rs185141197) and L150P (rs377741902) showed higher buried surface area (BSA) than wild-type. Following this, molecular dynamic (MD) simulation further affirmed the findings and revealed that T124I induced conformational changes in the irisin domain of FNDC5, which may significantly affect its binding with protein FGF21, potentially impairing synergistic effects of FNDC5 and FGF21 on adipocyte browning and increasing risk for developing obesity and related disorders.

Obesity-induced bone loss affects the life quality of patients all over the world. Irisin, one of the myokines, plays an essential role in bone and fat metabolism.

Investigate the effects of irisin on bone metabolism via adipocytes in the bone marrow microenvironment.

In this study, we fed fibronectin type III domain-containing protein 5 (FNDC5, the precursor protein of irisin) knockout mice (FNDC5-/-) with a high-fat diet (HFD) for 10 weeks. The quality of bone mass was assessed by micro-CT analysis, histological staining, and dynamic bone formation. In vitro, the lipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assayed by Oil Red O staining, and the osteogenic differentiation was assayed by alkaline phosphatase staining. Meanwhile, the gene expression in the BMSC-differentiated adipocytes by RNA sequence and the involved pathway of irisin were determined by western blot and qRT-PCR were performed.

The FNDC5-/- mice fed with a HFD showed an increased body weight, fat content of the bone marrow and bone, and a decreased bone formation compared with those with a standard diet (SD). In vitro, irisin inhibited the differentiation of BMSCs into adipocytes and alleviated the inhibition of osteogenesis derived from BMSCs by the adipocyte supernatant. RNA sequence and blocking experiment showed that irisin reduced the production of interleukin 6 (IL-6) in adipocytes through downregulating the TLR4/MyD88/NF-κB pathway. Immunofluorescence staining of bone marrow further confirmed an increased IL-6 expression in the FNDC5-/- mice fed with HFD compared with those fed with SD, which suffered serious bone loss.

Irisin downregulates activation of the TLR4/MyD88/NF-κB pathway, thereby reducing IL-6 production in adipocytes to enhance the osteogenesis of BMSCs. Thus, the rescue of osteogenesis of BMSCs, initially inhibited by IL-6, is a potential therapeutic target to mitigate obesity-induced osteoporosis.

Alzheimer's disease (AD) poses a significant obstacle in today's healthcare landscape, with limited effective treatments. Recent studies have revealed encouraging findings about how exercise-triggered irisin might help slow down the advancement of AD. Irisin, a myokine, released during physical activity, has garnered significant attention for its pleiotropic effects, extending beyond its traditional role in metabolic regulation. This review explores irisin's multifaceted potential in combating AD. Research indicates that irisin enhances synaptic plasticity, crucial for learning and memory, and exhibits neuroprotective properties that may slow AD progression by safeguarding neurons from degeneration. Additionally, irisin's ability to modulate inflammatory responses is significant, as neuroinflammation is a key feature of AD pathology. Irisin may also influence the metabolism and clearance of amyloid-beta plaques and tau tangles, hallmark pathological markers of AD. Furthermore, irisin boosts brain-derived neurotrophic factor expression, vital for neuronal health, and improves insulin glucose regulation, addressing impaired brain insulin signaling observed in AD. Exercise-induced irisin presents a non-pharmacological strategy, leveraging physical activity's brain health benefits. Future research should focus on elucidating irisin's mechanisms and conducting clinical trials to assess its therapeutic efficacy and safety in AD patients. Overall, irisin therapy offers a promising avenue for AD treatment, potentially slowing disease progression and enhancing cognitive function, paving the way for innovative therapeutic strategies in the fight against AD.

Myokines secreted from skeletal muscle such as irisin, osteokines secreted from bone such as osteocalcin, and hepatokines secreted from the liver such as fibroblast growth factor 21 (FGF21) play a role in the regulation of metabolic homeostasis. However, the changes that occur in obesity and the interaction between them have not been fully explained. Therefore, this study aimed to compare irisin, osteocalcin and FGF21 levels in young obese males against individuals with normal body weight and to reveal the possible relationship between them and with anthropometric measurements and blood lipid profile.

This single-center study included 28 Turkish young males aged 20-29 years: 14 obese participants with a body mass index (BMI) between 30.0 and 34.9 and 14 healthy controls with a BMI between 18.5 and 24.9. Anthropometric, and body composition parameters, blood lipid profile, and irisin, osteocalcin and FGF21 levels of groups were measured. Correlation analyses were performed between irisin, osteocalcin, and FGF21 and other measured parameters.

Circulating irisin, osteocalcin and FGF21 levels were significantly higher in the obese group than in the control group (p ​< ​0.05). Correlation analysis showed that irisin was positively correlated with total cholesterol, triglycerides and low density lipoprotein-cholesterol (LDL-C) and FGF21 was positively correlated with total cholesterol and LDL-C (p ​< ​0.05). Positive correlation between irisin and osteocalcin, FGF21 and osteocalcin and FGF21 and irisin was observed (p ​< ​0.05).

Irisin, osteocalcin, and FGF21 have a potential role in the pathophysiology of obesity and related metabolic diseases due to their interactions.

Doxorubicin (DOX), an anthracycline antibiotic, has limited clinical use due to its pronounced cardiotoxicity. Irisin, a myokine known for its metabolic regulation, has shown therapeutic effects on cardiovascular disease. This study investigates the potential cardioprotective function of irisin in reducing the cardiac injury induced by DOX.

In vitro, H9c2 cells were pretreated with irisin (20 nM) for 24 hours before exposure to DOX (1 μM). In vivo, C57BL/6 mice were administered DOX (5 mg/kg/week, i.p.) for 4 weeks, reaching a cumulative dose of 20 mg/kg. Irisin (1 mg/kg/ 3 days, i.p.) was administered to the mice both 7 days prior to and during DOX injection.Cardiac function was evaluated by echocardiography, and cardiac histology was assessed using HE, WGA, and Masson staining. Myocardial injury markers were quantified using ELISA, and apoptosis was analyzed via TUNEL staining. Oxidative stress was determined by measuring antioxidase activity, MDA and GSH levels, and DHE staining, while mitochondrial superoxide production was assessed using MitoSOX Red. Mitochondrial morphology and function evaluated using transmission electron microscopy and Seahorse analysis, respectively Inflammatory cytokines were quantified in serum and cell supernatants. The role of the PERK-eIF2α-ATF4 pathway mediated by irisin was investigated by Western blot. Using adeno-associated virus serotype-9 carrying mouse FNDC5 shRNA (AAV9-shFNDC5) further validated the protective role of irisin in DOX-induced myocardial injury.

Irisin reduced DOX-induced cardiac dysfunction and fibrosis. Moreover, irisin mitigated oxidative stress and inflammation through inhibiting the PERK-eIF2α-ATF4 pathway activated by DOX, thus preserving mitochondrial function. While cardiac FNDC5 knockdown exacerbated DOX-induced heart injury and PERK-eIF2α-ATF4 activation, which was partially reversed by irisin.

Irisin mitigates oxidative stress and inflammation by modulating the PERK-eIF2α-ATF4 pathway, highlighting its potential as a prospective approach for combating DOX-induced cardiotoxicity.

Preeclampsia is a pregnancy-specific disorder with unclear pathogenesis. Irisin, a recently identified exercise-induced factor, significantly influences lipid metabolism and cardiovascular function. Nonetheless, its role in trophoblast development during human placentation and the related intracellular signaling pathways remain poorly understood.

We assessed peripheral blood irisin expression in early pregnancy among patients with preeclampsia and its correlation with key clinical indicators. In trophoblast cell lines and mice, we used exogenous irisin and viral knockdown to investigate functional changes. Phosphorylation-specific antibody arrays and dual-luciferase reporter assays were used to explore downstream molecular mechanisms, which were subsequently validated in trophoblast cell lines and relevant gene knockout mice.

In early pregnancy, patients with preeclampsia exhibit decreased peripheral blood irisin levels, occurring earlier than traditional predictive markers, such as PLGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1). Furthermore, irisin concentration is positively correlated with proteinuria and abnormal blood pressure during pregnancy. Exogenous irisin significantly enhanced trophoblast cell migration, invasion, and proliferation while inhibiting apoptosis. It also increased STAT (signal transducers and activators of transcription) 4 phosphorylation and its binding to the GLUT (glucose transporter)-3 promoter, resulting in elevated GLUT-3 expression and glucose uptake in trophoblast cells. In vivo, increased peripheral irisin promoted embryo implantation, vascular remodeling, and enhanced glucose uptake, whereas reduced irisin resulted in a preeclampsia-like phenotype characterized by elevated blood pressure, proteinuria, renal-placental dysfunction, adipose accumulation, and restricted fetal growth.

Peripheral irisin improves preeclampsia by promoting embryo implantation and vascular remodeling through the activation of the STAT4/GLUT-3 pathway. Reduced peripheral irisin may contribute to preeclampsia-like pathologies. This study supports the advocacy for appropriate exercise during early pregnancy and provides new insights for preeclampsia prevention.

Aging is a complex biological process characterized by increased inflammation and susceptibility to various age-related diseases, including cognitive decline, osteoporosis, and type 2 diabetes. Exercise has been shown to modulate mitochondrial function, immune responses, and inflammatory pathways, thereby attenuating aging through the regulation of exerkines secreted by diverse tissues and organs. These bioactive molecules, which include hepatokines, myokines, adipokines, osteokines, and neurokines, act both locally and systemically to exert protective effects against the detrimental aspects of aging. This review provides a comprehensive summary of different forms of exercise for older adults and the multifaceted role of exercise in anti-aging, focusing on the biological functions and sources of these exerkines. We further explore how exerkines combat aging-related diseases, such as type 2 diabetes and osteoporosis. By stimulating the secretion of these exerkines, exercise supports healthy longevity by promoting tissue homeostasis and metabolic balance. Additionally, the integration of exercise-induced exerkines into therapeutic strategies represents a promising approach to mitigating age-related pathologies at the molecular level. As our understanding deepens, it may pave the way for personalized interventions leveraging physical activity to enhance healthspan and improve quality of life.

Developing effective drug screening methods for type 2 diabetes requires physiologically relevant models. Traditional 2D cell cultures have limitations in replicating in vivo conditions, leading to challenges in assessing drug efficacy. To overcome these issues, we developed a 3D artificial muscle model that induces insulin resistance, a hallmark of type 2 diabetes. Using C2C12 myoblasts cultured in a scaffold of 1% alginate and 1 mg/mL collagen type 1, we optimized conditions for differentiation and structural stability. Insulin resistance was induced using palmitic acid (PA), and glucose uptake was assessed using the fluorescent glucose analog 2-NBDG. The 3D model demonstrated superior glucose uptake responses compared with 2D cultures, with a threefold increase in insulin-stimulated glucose uptake on days 4 and 8 of differentiation. Induced insulin resistance was observed with 0.1 mM PA, which maintained cell viability and differentiation capacity. The model was validated through comparative drug screening using rosiglitazone and metformin, as well as 165 candidate compounds provided by Korea Chemical Bank. Drug screening revealed that three out of five hit compounds identified in both 2D and 3D models exhibited greater efficacy in 3D cultures, with results consistent with ex vivo assays using mouse soleus muscle. This model closely mimics in vivo conditions, offering a robust platform for type 2 diabetes drug discovery while supporting ethical research practices.

Ferroptosis is a regulated cell death mechanism distinct from apoptosis, autophagy, and necroptosis, marked by iron accumulation and lipid peroxidation. Since its identification in 2012, it has developed into a potential therapeutic target, especially concerning GI disorders like PC, HCC, GC, and CRC. This interest arises from the distinctive role of ferroptosis in the progression of diseases, presenting a new avenue for treatment where existing therapies fall short. Recent studies emphasize the promise of focusing on ferroptosis to fight GI cancers, showcasing its unique pathophysiological mechanisms compared to other types of cell death. By comprehending how ferroptosis aids in the onset and advancement of GI diseases, scientists aim to discover novel drug targets and treatment approaches. Investigating ferroptosis in gastrointestinal disorders reveals exciting possibilities for novel therapies, potentially revolutionizing cancer treatment and providing renewed hope for individuals affected by these tumors.

Oxidative stress (OS) injury is pivotal in acute pancreatitis (AP) pathogenesis, contributing to inflammatory cascades. Irisin, a ubiquitous cytokine, exhibits antioxidant properties. However, the role of irisin in AP remains inconclusive. Our study aims to elucidate irisin expression in AP patients and investigate its mechanism of action to propose a novel treatment strategy for AP. Serum irisin levels in 65 AP patients were quantified using an enzyme-linked immunosorbent assay and correlated with disease severity scores. Core genes implicated in AP-related oxidative stress were identified and screened via bioinformatics analysis. The therapeutic efficacy of irisin in AP was confirmed using a murine cerulein-induced AP model. The intrinsic mechanism of irisin's antioxidative stress action was investigated and verified in pancreatic AR42J cells (Supplementary Fig. 1). Common targets shared by irisin and AP were further validated using a molecular docking model which was constructed for virtual docking analysis. This study investigated alterations in redox status in AP and found a significant reduction in serum irisin levels, correlating inversely with AP severity. In a murine AP model, we showed that irisin triggers an antioxidative stress program via the KEAP1 gene; this process helps reestablish redox balance by decreasing the buildup of reactive oxygen species (ROS) and suppressing the secretion of inflammatory mediators within pancreatic tissues Notably, increased KEAP1 expression counteracted the antioxidative effects of irisin. Our findings unveil a novel therapeutic mechanism for AP, wherein irisin inhibits KEAP1 to alleviate OS. Increasing irisin levels in vivo presents a promising strategy for AP treatment.

Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin in in vitro models of MM cells (HBLwt/wt, LND1wt/wt, Hmel1V600K/wt and M3V600E/V600E) capable of the oncogenic activation of BRAF. We treated MM cells with different concentrations of r-irisin (10 nM, 25 nM, 50 nM, 100 nM) for 24 h-48 h. An MTT assay highlighted that r-irisin did not affect the proliferation of MM cells. We subsequently treated MM cells with 10 nM r-irisin, corresponding to the dose exhibiting biological activity in vitro. Irisin reduced the invasive ability of only LND1wt/wt (p < 0.05), which highly expressed αv gene levels, but did not affect the invasion of BRAFmut cells. Gelatin zymography analysis showed a reduction in the enzymatic activity of MMP-2 and MMP-9 in BRAFwt/wt cells treated with 10 nM r-irisin. Moreover, gene expression analysis (qPCR) of MMP-2 and MMP-9 and of the fibrinolytic system (uPAR, uPA and PAI-1) highlighted a crucial role of 10 nM r-irisin treatment in the inhibition of pro-invasive systems in BRAFwt/wt. In conclusion, our results may suggest a possible differential role of irisin in melanoma cells.

Despite all the advances in our knowledge regarding obesity, our understanding of its etiology is still far from complete. This study aimed to evaluate the association of serum irisin levels with physical activity and some of the metabolic syndrome-related biomarkers among obese people with low-calorie intake and non-obese people with high-calorie intake.

Obese and non-obese healthy individuals with respectively low and high-calorie intakes were recruited. Irisin and other biomarkers were measured using standard biochemical methods. Participants' physical activity was evaluated by administering the International Physical Activity Questionnaire (IPAQ). To analyze the body composition of the participants, a standard body composition device (ioi 353) was applied. Logistic regression was used to calculate the odds ratio (OR) and to examine the effect of confounders such as age, sex, genetics, and activity.

Data from the seventy-seven participants were included in the final analysis. The mean age of the participants in the obese and non-obese groups was 38.33 ± 14.88 and 30.24 ± 13.37 years, respectively. Participants in the obese group had lower physical activity compared to the non-obese group (3395.38 ± 2801 MET-min/week vs. 6015.18 ± 3178 MET-min/week; p < 0.001). The Irisin concentration in the obese and non-obese groups was 7.84 ± 2.49 ng/ml and 8.06 ± 1.89 ng/ml, respectively, which wasn't significantly different (p = 0.66). We observed a noteworthy and favorable association between irisin concentration and total body water (TBW), lean body mass (LBM), and soft lean mass (SLM) in the non-obese group.

These data indicated that although obese participants were relatively inactive compared to non-obese individuals, circulating irisin level wasn't significantly different between the two groups.

Irisin, a hormone-like adipo-myokine, has garnered considerable attention in recent years for its potential impact in metabolic diseases. Its physiological effects are similar to those of thyroid hormones, prompting numerous investigations into potential correlations and interactions between irisin and thyroid function through various in vitro and animal experiments. However, existing studies suggest that the relationship between irisin and thyroid diseases is highly complex and multifaceted. In this paper, we have summarized the research results on serum irisin and thyroid function, providing an overview of advancements and constraints in current research on irisin and thyroid hormones. The aim is to offer insights and directions for future clinical trials in this field.

Irisin-based interventions have gained attention for their potential to modulate the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in various diseases. Physiologically, irisin is a myokine released during physical exercise that exerts anti-inflammatory effects and is a metabolic and cardiometabolic enhancer. On the other hand, AMPK is crucial for maintaining energy balance and metabolic homeostasis. Therefore, individuals presenting low blood levels of irisin and AMPK dysregulation are more predisposed to metabolic disorders and cardiovascular health inflammatory conditions since regulating energy balance and metabolic homeostasis are crucial for preventing or treating these disorders. In light of those mentioned above and considering that no review has addressed the intricate relationships between irisin and AMPK regulation in the realm of metabolic disorders, cardiovascular health, and inflammatory conditions, we comprehensively reviewed studies involving irisin's effects on AMPK signaling in different models and interventions. Our systematic analysis involved in vitro studies, animal models, and their relevant clinical implications of irisin targeting AMPK due to the absence of relevant clinical trials. The outcomes and limitations of the included studies were extensively highlighted. Objectively, irisin improved metabolic disorders by enhancing β-cell function and insulin secretion in diabetes, mitigating myocardial injury in cardiovascular conditions, and reducing inflammation and oxidative stress in various injury models by targeting AMPK. However, the lack of clinical trials limits the generalizability of these findings to human subjects. Future research should focus on translating these findings into clinical applications and exploring the broader implications of irisin-based interventions in human health.

A high-fat diet and physical inactivity are key contributors to obesity, predisposing individuals to various chronic diseases, such as cardiovascular disease and diabetes, which involve multiple organs and tissues. To better understand the role of multi-organ interaction mechanisms in the rising incidence of obesity and its associated chronic conditions, treatment and prevention strategies are being extensively investigated. This review examines the signaling mechanisms between different tissues and organs, with a particular focus on the crosstalk between adipose tissue and the muscle, brain, liver, and heart, and potentially offers new strategies for the treatment and management of obesity and its complications.

Current research suggests that irisin is closely linked to the pathogenesis and progression of metabolic dysfunction-associated fatty liver disease (MAFLD). This systematic review and meta-analysis updates our previous meta-analysis and further explores the relevance between circulating irisin levels and MAFLD.

Nine databases (PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, Weipu, CBM, Clinicaltrials.gov and gray literature) were retrieved as of 1st August, 2024. The standardized mean difference (SMD) and 95% confidence interval (CI) represent pooled effect size. We used the Newcastle-Ottawa Scale to evaluate the quality of articles and the certainty of evidence assessed by GRADE system. All statistical analyses were performed using RevMan 5.3 and Stata 12(Stata Corporation, yi TX).

Fifteen case-control studies were included. Circulating irisin levels in the MAFLD group were markedly lower than those in the healthy group (SMD=-1.04 [-1.93, -0.14]). Subgroup analyses by race, age, severity and T2DM revealed that circulating irisin levels were lower in the MAFLD group compared to those in the healthy controls in the Asian population (SMD=-1.38 [-2.44, -0.31], P<0.05) and in those above 50 years old (SMD=-2.23 [-3.64, -0.81], P<0.05) and higher in the mild MAFLD groups than those in moderate to severe MAFLD groups (SMD = 11.68 [9.05, 14.31], P<0.05). And the circulating irisin levels in MAFLD patients with T2DM were significantly lower than those in healthy group (SMD = -2.90 [-4.49, -1.30]). ELISA kits from different companies also presented different relationships.

There were significantly lower circulating irisin levels in the MAFLD group than in the healthy control group. Although these results differed from our previous results, there is no denying that circulating irisin levels are closely associated with the advancement of MAFLD.

Irisin, a fibronectin III protein secreted by muscles during physical exercise, plays a significant role in the browning of white fat and cell adhesion, highlighting the importance of its conformational transitions. In this study, we investigated the folding and unfolding dynamics of a single irisin domain using a single-molecule manipulation technique known as magnetic tweezers. In addition to the native state, irisin can also fold transiently into a misfolded state. We determined the folding free energies of the native and misfolded states as well as their force-dependent folding and unfolding rates. The free energy of the misfolded state is higher than that of the unfolded state, and the misfolded state has a homogeneous force-dependent unfolding rate. The stable native state demonstrates heterogeneous unfolding rates that are within ∼1 order of magnitude. Via comparison with the well-studied 10th fibronectin III domain that has a partially folded intermediate state, our study demonstrates that proteins with similar structure can have distinct folding pathways.

Background and objective There is growing concern regarding metabolic and inflammatory disorders globally, underscoring the need for effective nonpharmacological interventions. Irisin, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and leptin are biomarkers of metabolic and inflammatory health. In this study, we aimed to investigate the comparative effects of basil seed supplementation or endurance exercise on biomarkers of chronic oxidative stress. Methods This prospective observational study enrolled 60 participants who were randomly divided into two groups: Group A (basil seeds, n=30) and Group B (endurance exercise, n=30). Participants in Group A consumed 10 grams of soaked basil seeds daily for eight weeks, while those in Group B underwent a supervised endurance exercise regimen (45 minutes/day, five days/week). Biomarkers, including irisin, IL-6, TNF-α, and leptin, were quantified using enzyme-linked immunosorbent assay (ELISA) both at baseline and post-intervention. Within-group and between-group differences were analyzed using paired and independent t-tests, with a significance threshold of p<0.05. Results Overall, the baseline characteristics in Group A (age: 35.4 ± 5.0 years; BMI: 24.5 ± 2.3 kg/m²) and B (age: 34.9 ± 4.8 years; BMI: 24.9 ± 2.4 kg/m²) were comparable (p>0.05). Significant changes were observed in both groups post-intervention. Irisin levels increased moderately in group A (47.23 ± 4.8 µg/mL to 50.79 ± 5.13 µg/mL, p<0.01), and IL-6, TNF-α, and leptin decreased (IL-6: 28.2 ± 2.13 pg/mL to 18.1 ± 2.01 pg/mL, p<0.01; TNF-α: 34.5 ± 2.72 pg/mL to 23.6 ± 2.64 pg/mL, p<0.01; and leptin: 8.4 ± 1.96 ng/mL to 3.9 ± 0.83 ng/mL, p<0.01). Group B showed a significant increase in irisin (44.04 ± 3.58 µg/mL to 150.1 ± 9.32 µg/mL, p<0.001) and a non-significant rise in IL-6 (31.65 ± 2.4 pg/mL to 35.64 ± 3.17 pg/mL, p>0.05). TNF-α levels increased in Group B (31.65 ± 3.27 pg/mL vs. 61.66 ± 3.85 pg/mL, p<0.001) and decreased in Group A, while leptin levels slightly decreased in Group B (7.94 ± 1.27 ng/mL vs. 4.19 ± 0.64 ng/mL, p>0.05). Conclusions Supplementation with basil seed and exercise training with endurance exercise had distinct effects on biomarkers of metabolism and inflammation. Irisin levels were significantly improved by endurance exercise, while basil seeds were most effective in reducing IL-6, TNF-α, and leptin. The findings suggest that basil seeds and exercise provide synergistic effects against metabolic and inflammatory diseases.

One of the key functions of brown adipose tissue is its positive impact on metabolism. This study aimed to examine the potential involvement of brown fat-related hormones in the development of metabolically healthy obesity. Specifically, we sought to compare the levels of NRG4, FGF21, and irisin between metabolically healthy and unhealthy individuals with obesity.

Patients with BMI ≥ 30 kg/m2 and aged between 20 and 50 years were included in the study. Among these patients, those who did not have any metabolic syndrome criteria except for increased waist circumference were defined as metabolically healthy obese. Age, gender, BMI, body fat, and muscle mass, matched metabolically healthy and unhealthy obese groups were compared in terms of FGF21, irisin, and NRG4 levels.

Metabolically healthy and unhealthy obese groups were similar in terms of age and gender. There was no difference between the two groups in terms of BMI, weight, total body fat, muscle, fat-free mass, distribution of body fat and muscle mass. No statistically significant difference was found between irisin, NRG4, and FGF21 levels between metabolically healthy and unhealthy individuals with obesity. It was found that irisin had a significant inverse correlation with BMI and body fat percentage.

The present study showed no difference between metabolically healthy and unhealthy obese individuals in terms of irisin, FGF21, and NRG4 levels. The weak association between irisin and BMI and body fat percentage may suggest a potential link between irisin with metabolic health.

Limited data exist regarding the impact of exercise intensity on irisin release and its association with insulin sensitivity in individuals of differing obesity status. The objective of this study was to investigate the impact of exercise intensity on the acute release of irisin in healthy-weight individuals and individuals with obesity, and whether irisin release during acute exercise was associated with greater insulin sensitivity across obesity status. A randomized controlled crossover study was conducted on 26 non-overweight/obese (non-OW/OB) (BMI: 22.2 ± 1.5  kg/m2) and 26 overweight/obese (OW/OB) (BMI: 33.9 ± 6.5  kg/m2) adults who performed an acute bout of moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), and rest. Irisin was quantified via ELISA and western blotting, and insulin sensitivity (Si) was estimated using the Matsuda index. OW/OB displayed a significantly lower level of circulating irisin and protein expression compared to non-OW/OB (p < 0.01). Insulin sensitivity was positively correlated with irisin release during MICT and HIIT in non-OW/OB (all p < 0.05), but not in OW/OB. Regarding irisin expression, non-OW/OB with high Si had a 2.03-fold (p < 0.05) increase during HIIT, while OW/OB with high Si had only a 1.54-fold increase (p < 0.05). These results suggest that irisin is released differently according to obesity status and varying exercise intensities. OW/OB individuals have a blunted irisin response to acute exercise and lower baseline irisin concentrations compared to non-OW/OB individuals. Although exercise stimulates irisin release in non-OW/OB individuals, only a greater exercise intensity stimulates irisin release in OW/OB individuals. These findings are clinically relevant, as irisin is associated with greater insulin sensitivity. This trial was registered at clinicaltrials.gov (NCT03514238).

Introduction: Circuit training is a form of body conditioning with endurance and resistance components. Given the function of skeletal muscle as an endocrine organ secreting various myokines involved in maintaining glucose metabolism homeostasis, our study focused on estimating the impact of the implemented training program on the direction of changes in myokines such as interleukin (IL)-6, IL-10, fibroblast growth factor 21 (FGF21), and irisin in women newly diagnosed with insulin resistance. Methods: This prospective controlled trial randomly divided 42 women into two groups. The training group performed circuit training combining strength (50%-80% of one-repetition maximum) and endurance (50%-75% of heart rate reserve) exercises for 3 months, three 33-min sessions weekly. Exercises were performed on five weight and two cardio machines. The control nontraining group did not change their previous activity. Body composition indicators and IL-6, IL-10, FGF21, and irisin levels were measured before and after the intervention. The data for 27 patients were analysed using two-way repeated measures analyses of variance. Results: The pattern of change in serum IL-6 levels over time differed significantly between the groups (p < 0.05). The patterns of change did not differ significantly between groups for IL-10, FGF21, and irisin. Conclusion: The circuit training program implemented in women newly diagnosed with insulin resistance significantly increased their serum IL-6 and not their IL-10, FGF21, and irisin levels. Trial Registration: ClinicalTrials.gov: NCT04528693.

This review explores the dual role of skeletal muscle as both a mechanical and endocrine organ, highlighting its contributions to overall health and its adaptability to various inputs such as nutrition, hormones, exercise, and injuries. In addition to its role in metabolism and energy conversion, skeletal muscle secretes signalling molecules called myokines (at rest) and exerkines (during/after physical exercise), which communicate with other organs like the brain, the cardiovascular system, and the immune system. Key molecules such as interleukins, irisin, and myostatin are discussed for their roles in mediating muscle health and inter-organ communication. This work also focuses on the muscle-gut axis, emphasising the bidirectional interaction between skeletal muscle and the gut microbiota, a complex ecosystem influencing immune defence, digestion, and metabolism. Muscle activity, particularly exercise, alters the gut microbial composition, promoting beneficial species, while gut-derived metabolites like short-chain fatty acids (SCFAs) impact muscle metabolism, mitochondrial function, and insulin sensitivity. Dysbiosis, or an imbalanced microbiota, can lead to muscle atrophy, inflammation, and metabolic dysfunction. This evidence highlights emerging research into myokines and exerkines as potential therapeutic targets for managing conditions like muscle decline, ageing, and metabolic diseases through muscle-gut interactions.

Dysregulation of chondrogenic differentiation is associated with osteoarthritis (OA). The myokine irisin is beneficial in OA treatment; yet, the underlying mechanism is not fully understood. Long noncoding RNAs (lncRNAs) act as important regulators of chondrocyte differentiation. This study was conducted to address the role of lncRNAs in mediating irisin-induced chondrocyte differentiation.

We investigated the irisin-regulated lncRNA profile change in human mesenchymal stem cells (MSCs) using published whole transcriptome sequencing data. We predicted their potential targets and competitive endogenous RNA (ceRNA) prediction and analyzed their molecular functions using functional enrichment analysis.

More differentially expressed lncRNAs (DElncRNAs) were observed in irisin-treated samples. The top irisin-induced lncRNAs were associated with OA or chondrogenic differentiation, including XIST, PAX8-AS1, CASC15, LINC01618, and DLX6-AS1. The DEGs co-expressed with DElncRNAs were enriched in skeletal system development, extracellular matrix (ECM) organization, cell adhesion, and inflammation associated pathways. Several lncRNAs likely acted as ceRNAs to regulate downstream mRNAs including ROR2 and SORBS1 in in OA or chondrogenic differentiation.

We demonstrate the global regulation of lncRNAs by irisin during chondrogenic differentiation of human MSCs. Further study is required to characterize the key irisin-regulated lncRNAs in chondrogenic differentiation.

Diabetes-induced neuropathy represents a major etiology of dementia, highlighting an urgent need for the development of effective therapeutic interventions. In this study, we explored the role of fibronectin type III domain containing 5 (FNDC5)/Irisin in mitigating hyperglycemia-induced neurotoxicity in HT22 cells and investigated the underlying mechanisms. Our findings reveal that high glucose conditions are neurotoxic, leading to reduced viability of HT22 cells and increased apoptosis. Furthermore, the elevated expression of the intracellular ferroptosis marker Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), along with increased levels of ferrous ions and malondialdehyde (MDA), suggests that high glucose conditions may induce ferroptosis in HT22 cells. FNDC5/Irisin treatment effectively mitigates high glucose-induced neurotoxicity and ferroptosis in HT22 cells. Mechanistically, FNDC5/Irisin enhances cellular antioxidant capacity, regulates ACSL4 expression, and improves intracellular redox status, thereby inhibiting ferroptosis and increasing HT22 cell survival under high-glucose conditions. These results highlight the neuroprotective potential of FNDC5/Irisin in high glucose environments, offering a promising avenue for developing treatments for diabetes-related neurodegenerative diseases.

Myokines, bioactive peptides released by skeletal muscle, have emerged as crucial regulators of metabolic and protective pathways in peripheral tissues, particularly in combating oxidative stress and inflammation. Their plasma concentration significantly increases following exercise, offering valuable insights into the role of physical activity in preventing sarcopenia and mitigating metabolic diseases, including obesity, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). This review focuses on discussing the roles of specific myokines in activating intracellular signaling pathways within the liver, which confer protection against steatosis and lipid peroxidation. We detail the mechanism underlying lipid peroxidation and highlight the liver's antioxidant defenses, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), which are pivotal in reducing ferroptosis. Furthermore, we provide an in-depth analysis of key myokines, including myostatin, brain-derived neurotrophic factor (BDNF), and irisin, among others, and their potential impact on liver function. Finally, we discuss the molecular mechanisms through which these myokines influence oxidate stress and lipid metabolism, emphasizing their capacity to modulate antioxidant responses in the liver. Finally, we underscore the therapeutic potential of exercise as a non-pharmacological intervention to enhance myokine release, thereby preventing the progression of MASD through improved hepatic antioxidant defenses. This review represents a comprehensive perspective on the intersection of exercise, myokine biology, and liver health.

Fibronectin type III domain-containing protein 5 (FNDC5) exerts potential anti-arrhythmic effects. However, the function and mechanism of FNDC5 in diabetes-associated atrial fibrillation (AF) remain unknown. In this study, bioinformatics analysis, in vivo and in vitro experiments were conducted to explore the alteration and role of FNDC5 in diabetes-related atrial remodeling and AF susceptibility. RNA sequencing data from atrial samples of permanent AF patients and diabetic mice exhibited significantly decreased FNDC5 at the transcriptional level, which was in line with the protein expression in diabetic mice as well as high glucose and palmitic acid (HG+PA) injured atrial myocytes. Diabetic mice exhibited adverse atrial remodeling and increased AF inducibility. Moreover, reduced atrial FNDC5 was accompanied with exacerbated NOD-like receptor pyrin domain containing 3 (NLRP3) activation and disturbed mitochondrial fission and fusion processes, as evidenced by decreased expressions of optic atrophy 1 (OPA-1), mitofusin (MFN-1, MFN-2) and increased phosphorylation of dynamin-related protein 1 (Ser616). These effects were validated in HG+PA-treated atrial myocytes. Critically, FNDC5 overexpression remarkably enhanced cellular antioxidant capacity by upregulating the expressions of superoxide dismutase (SOD1, SOD2) level. In addition, HG+PA-induced mitochondrial dysfunction was ameliorated by FNDC5 overexpression as evidenced by improved mitochondrial dynamics and membrane potential. Moreover, NLRP3 inflammasome-mediated inflammation was reduced by FNDC5 overexpression, and AMPK signaling might serve as the key down-stream effector. The present study demonstrated that reduced atrial FNDC5-AMPK signaling contributed to the pathogenesis of diabetes- associated AF by impairing mitochondrial dynamics and activating the NLRP3 inflammasome. These findings provide promising therapeutic avenues for diabetes-associated AF.

Metabolic syndrome (MetS) is a prevalent public health problem. Uric acid (UA) is increased by MetS. We investigated whether administration of UA and 10% fructose (F) would accelerate MetS formation and we also determined the effects of irisin and exercise. We used seven groups of rats. Group 1 (control); group 2 (sham); group 3 (10% F); group 4 (1% UA); group 5 (2% UA); group 6 (10% F + 1% UA); and Group 7, (10% F + 2% UA). After induction of MetS (groups 3 -7), Group 3 was divided into three subgroups: 3A, no further treatment; 3B, irisin treatment; 3C, irisin treatment + exercise. Group 4, 1% UA, which was divided into three subgroups: 4A, no further treatment; 4B, irisin treatment; 4C, Irisin treatment + exercise. Group 5, 2% UA, which was divided into three subgroups: 5A, no further treatment; 5B, irisin treatment; 5C, irisin treatment + exercise. Group 6, 10% F + 1% UA, which was divided into three subgroups: 6A, no further treatment; 6B, irisin treatment; 6C, irisin treatment + exercise. Group 7, 10% F + 2% UA, which was divided into three subgroups: 7A, no further treatment; 7B, irisin treatment; 7C, irisin treatment + exercise., İrisin was administered 10 ng/kg irisin intraperitoneally on Monday, Wednesday, Friday, Sunday each week for 1 month. The exercise animals (in addition to irisin treatment) also were run on a treadmill for 45 min on Monday, Wednesday, Friday, Sunday each week for 1 month. The rats were sacrificed and samples of liver, heart, kidney, pancreas, skeletal muscles and blood were obtained. The amounts of adropin (ADR) and betatrophin in the tissue supernatant and blood were measured using an ELISA method. Immunohistochemistry was used to detect ADR and betatrophin expression in situ in tissue samples. The duration of these experiments varied from 3 and 10 weeks. The order of development of MetS was: group 7, 3 weeks; group 6, 4 weeks; group 5, 6 weeks; group 4, 7 weeks; group 3, 10 weeks. Kidney, liver, heart, pancreas and skeletal muscle tissues are sources of adropin and betatrophin. In these tissues and in the circulation, adropin was decreased significantly, while betatrophin was increased significantly due to MetS; irisin + exercise reversed this situation. We found that the best method for creating a MetS model was F + UA2 supplementation. Our method is rapid and simple. Irisin + exercise was best for preventing MetS.

This study aimed to evaluate the roles of galectin-3 and irisin as biomarkers in predicting severe outcomes in COVID-19 patients.

We analyzed serum levels of galectin-3 and irisin in 59 patients with severe COVID-19 and 30 healthy controls. Elevated galectin-3 levels were associated with increased risks of mortality, need for intensive care, and severe acute respiratory distress syndrome. The optimal cut-off value for galectin-3 was 13.47 ng/ml, with a sensitivity of 72.7% and specificity of 76.6%. Irisin levels did not differ significantly between survivors and non-survivors at admission or on the 3rd day post-admission, but approached significance on the 7th day. These findings suggest that galectin-3 could be a valuable prognostic biomarker for severe COVID-19 outcomes, while irisin's role remains to be clarified in further studies.

The correlation between type 2 diabetes mellitus (T2DM) and the occurrence of liver fibrosis is well-established. However, the longitudinal association between body composition and liver fibrosis progression in patients with T2DM remains incompletely explored.

Total of 390 patients with T2DM underwent body composition assessments, followed by a median duration of 2.13 years. The calculated parameters included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F) and appendicular skeletal muscle mass/trunk fat mass ratio (A/T). Liver fibrosis was evaluated through liver stiffness measurement (LSM). Patients were classified according to BMI and body composition, followed by a comprehensive investigation into the impact of body composition changes on liver fibrosis outcomes.

Among 72 patients with incident advanced liver fibrosis at readmission, ΔBMI, ΔFMI and ΔTFMI increased, while ΔM/F and ΔA/T decreased. Individuals who kept obese had a dramatically elevated hazard of incident advanced liver fibrosis compared to those who kept non-obese, with an adjusted odds ratio of 3.464. When TFMI heightened, the hazard of incident advanced liver fibrosis was 3.601 times higher compared to the decreased group. Additionally, individuals in increased ASMI and A/T groups showed a slight advantage in preventing incident advanced liver fibrosis compared to the stable groups.

Stable obesity was associated with a greater hazard of liver fibrosis advancement, and an increase in TFMI may promote the progression of liver fibrosis. Maintaining a balanced muscle/fat ratio appeared to help prevent the progression.

Neuroinflammation is a major feature of type 2 diabetic mellitus (T2DM), adversely affecting hippocampal neurogenesis. However, the precise mechanism is not fully understood, and therapeutic approaches are currently lacking. Therefore, we determined the effects of exercise on neuroinflammation and hippocampal neurogenesis in T2DM mice, with a specific focus on understanding the role of the irisin and related cascade pathways in modulating the beneficial effects of exercise in these processes. Ten-week exercise significantly decreased T2DM-induced inflammation levels and markedly promoted hippocampal neurogenesis and memory function. However, these positive effects were reversed by 10 weeks of treatment with cyclo RGDyk, an inhibitor of irisin receptor signaling. Additionally, exercise helped reduce the M1 phenotype polarization of hippocampal microglia in diabetic mice; this effect could be reversed with cyclo RGDyk treatment. Moreover, exercise markedly increased the levels of fibronectin type III domain-containing protein 5 (FNDC5)/irisin protein while decreasing the expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and nuclear factor kappa-B (NF-κB) in the hippocampus of T2DM mice. However, blocking irisin receptor signaling counteracted the down-regulation of TLR4/MyD88/NF-κB in diabetic mice undergoing exercise intervention. Conclusively, exercise appears to be effective in reducing neuroinflammation and enhancing hippocampal neurogenesis and memory in diabetes mice. The positive effects are involved in the participation of the irisin/TLR4/MyD88/NF-κB signaling pathway, highlighting the potential of exercise in the management of diabetic-induced cognitive decline.