Search Results (1,128)

Circadian rhythms are intrinsic 24 h cycles that regulate metabolic processes across multiple tissues, with skeletal muscle emerging as a central node in this temporal network. Muscle clocks govern gene expression, fuel utilisation, mitochondrial function, and insulin sensitivity, thereby maintaining systemic energy homeostasis. However, circadian misalignment, whether due to behavioural disruption, nutrient excess, or metabolic disease, impairs these rhythms and contributes to insulin resistance, and the development of obesity, and type 2 diabetes mellitus. Notably, the muscle clock remains responsive to non-photic cues, particularly exercise, which can reset and amplify circadian rhythms even in metabolically impaired states. This work synthesises multi-level evidence from rodent models, human trials, and in vitro studies to elucidate the role of skeletal muscle clocks in circadian metabolic health. It explores how exercise entrains the muscle clock via molecular pathways involving AMPK, SIRT1, and PGC-1α, and highlights the time-of-day dependency of these effects. Emerging data demonstrate that optimally timed exercise enhances glucose uptake, mitochondrial biogenesis, and circadian gene expression more effectively than time-agnostic training, especially in individuals with metabolic dysfunction. Finally, findings are integrated from multi-omic approaches that have uncovered dynamic, time-dependent molecular signatures that underpin circadian regulation and its disruption in obesity. These technologies are uncovering biomarkers and signalling nodes that may inform personalised, temporally targeted interventions. By combining mechanistic insights with translational implications, this review positions skeletal muscle clocks as both regulators and therapeutic targets in metabolic disease. It offers a conceptual framework for chrono-exercise strategies and highlights the promise of multi-omics in developing precision chrono-medicine approaches aimed at restoring circadian alignment and improving metabolic health outcomes. Full article

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

The enteroendocrine system of the gastrointestinal (GI) tract is the largest endocrine organ in the human body, playing a central role in the regulation of hunger, satiety, digestion, and energy homeostasis. Numerous factors—including dietary components, physical activity, and the gut microbiota—affect the secretion of GI hormones. This study aims to analyze how these factors modulate enteroendocrine function and influence systemic metabolic regulation. This review synthesizes the current scientific literature on the physiology and distribution of enteroendocrine cells and mechanisms of hormone secretion in response to macronutrients, physical activity, and microbial metabolites. Special attention is given to the interactions between gut-derived signals and central nervous system pathways involved in appetite control. Different GI hormones are secreted in specific regions of the digestive tract in response to meal composition and timing. Macronutrients, particularly during absorption, stimulate hormone release, while physical activity influences hormone concentrations, decreasing ghrelin and increasing GLP-1, PYY, and leptin levels. The gut microbiota, through fermentation and metabolite production (e.g., SCFAs and bile acids), modulates enteroendocrine activity. Species such as Akkermansia muciniphila are associated with improved gut barrier integrity and enhanced GLP-1 secretion. These combined effects contribute to appetite regulation and energy balance. Diet composition, physical activity, and gut microbiota are key modulators of gastrointestinal hormone secretion. Their interplay significantly affects appetite regulation and metabolic health. A better understanding of these relationships may support the development of personalized strategies for managing obesity and related disorders. Full article

Obesity remains a major global health challenge with limited therapeutic options. Bromelain, a proteolytic enzyme complex derived from pineapple, has been recognized for its natural anti-inflammatory, anti-edematous, and appetite-suppressing properties. This study aimed to investigate the effects of bromelain on hypothalamic neuropeptides and metabolic markers in a high-fat diet (HFD)-induced obesity model in rats. Thirty-six male Wistar albino rats were randomly divided into four groups: standard diet (SD), standard diet with bromelain (SDBro), high-fat diet (HFD), and high-fat diet with bromelain (HFDBro). Obesity was induced by a 3-month HFD regimen, followed by bromelain supplementation (200 mg/kg/day, orally) for one month. Hypothalamic tissues were analyzed via ELISA for neuropeptide Y (NPY), pro-opiomelanocortin (POMC), glucose transporter 2 (GLUT2), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 receptor (IGF1R). While NPY levels showed no significant changes, POMC increased in the HFD and was normalized with bromelain. GLUT2 was downregulated in the HFD and significantly restored by bromelain. FGF2 levels remained unchanged. IGF1R was upregulated in the HFD but reduced by bromelain, with an unexpected increase in SDBro. Overall, bromelain partially reversed HFD-induced disruptions in hypothalamic energy-regulating pathways, particularly affecting GLUT2 and POMC. These findings highlight bromelain’s potential role in central metabolic regulation under dietary stress. Full article

Background/Objectives: Prioritizing diet- or exercise-related self-efficacy and social support with their interactions may improve the effectiveness of interventions aimed at increasing daily fruit/vegetable intake and exercise, thereby reducing the risk of metabolic disorders in abdominally obese women. This study aimed to identify the profiles of diet- or exercise-related self-efficacy and social support among women with abdominal obesity, examine profiles related to insufficient fruit/vegetable intake and exercise, and explore associating factors of these profiles. Methods: A cross-sectional investigation in central south mainland China collected sociodemographic, anthropometric, and health-related variables, diet-related self-efficacy (Diet-SE) and social support (Diet-SS), exercise-related self-efficacy (Exercise-SE) and social support (Exercise-SS), and daily fruit/vegetable intake and exercise. We used latent profile analysis to identify distinct profiles, and binary logistic regression to examine the profiles’ behaviors and associating factors. Results: A total of 327 abdominally obese women were categorized into four profiles of Diet-SE and Diet-SS, and five profiles of Exercise-SE and Exercise-SS. Women in the Diet Dual-Low Group were associated with insufficient daily fruits/vegetables intake. Women in the Exercise Dual-Low Group or Exercise-SS Medium–Low Group were more likely to engage in insufficient daily exercise. Conclusions: Our findings align with previous evidence that women with low diet- or exercise-related self-efficacy and social support are at increased risk for insufficient daily fruit/vegetable intake or exercise. Additionally, medium Exercise-SS is associated with insufficient exercise behaviors, suggesting that interventions targeting healthy exercise should be initiated earlier among women with medium Exercise-SS, rather than waiting for it to decline to low level. Full article

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Risk factors for EC include metabolic alterations (obesity, metabolic syndrome, insulin resistance), hormonal imbalance, age at menopause, reproductive factors, and inherited conditions, such as Lynch syndrome. For the inherited forms, several genes had been implicated in EC occurrence and development, such as POLE, MLH1, TP53, PTEN, PIK3CA, PIK3R1, CTNNB1, ARID1A, PPP2R1A, and FBXW7, all mutated at high frequency in EC patients. However, gene function impairment is not necessarily caused by mutations in the coding sequence of these and other genes. Gene function alteration may also occur through post-transcriptional control of messenger RNA translation, frequently caused by microRNA action, but transcriptional impairment also has a profound impact. Here, we review how chromatin modifications change the expression of genes whose impaired function is directly related to EC etiopathogenesis. Chromatin modification plays a central role in EC. The modification of chromatin structure alters the accessibility of genes to transcription factors and other regulatory proteins, thus altering the intracellular protein amount. Thus, DNA structural alterations may impair gene function as profoundly as mutations in the coding sequences. Hence, its central importance is in the diagnostic and prognostic evaluation of EC patients, with the caveat that chromatin alteration is often difficult to identify and needs investigations that are specific and not broadly used in common clinical practice. The different phases of the healthy endometrium menstrual cycle are characterized by differential gene expression, which, in turn, is also regulated through epigenetic mechanisms involving DNA methylation, histone post-translational modifications, and non-coding RNA action. From a medicolegal and policy-making perspective, the implications of using epigenetics in cancer care are briefly explored as well. Epigenetics in endometrial cancer is not only a topic of biomedical interest but also a crossroads between science, ethics, law, and public health, requiring integrated approaches and careful regulation. Full article

Pleurotus eryngii is an edible mushroom with previously characterized β-glucans. Its potential to ameliorate postprandial glycemia and regulate appetite at the postprandial state has been previously shown. However, its effect on protein digestion remains unexplored. We aimed to investigate the effect of baked P. eryngii with a known β-glucan content (4.5 g) on plasma free amino acids of patients with central obesity and metabolic abnormalities at a postprandial state. In this acute, randomized controlled cross-over study, thirteen healthy male volunteers consumed one meal that was prepared with P. eryngii and one control meal; each meal was separated by one month. Blood was collected, and plasma was isolated at different timepoints before and after the consumption. Gas chromatography–mass spectrometry was used to quantify 24 free amino acids in the plasma samples. The area under the curve with respect to increase (AUCi) was computed, and the AUCi for aromatic amino acids was found to be higher after the consumption of the control meal compared to the P. eryngii meal (p = 0.027 for phenylalanine, p = 0.008 for tyrosine, and p = 0.003 for tryptophan). The above novel findings suggest that the β-glucans present in P. eryngii mushrooms are potential modulators of AA release into the bloodstream. Full article

Background: Metabolic syndrome (MetS) is a multifactorial condition involving central obesity, dyslipidemia, hypertension, and impaired glucose metabolism, significantly increasing the risk of type 2 diabetes and cardiovascular disease. Objectives: Given the clinical heterogeneity of MetS, this study aimed to identify distinct metabolic phenotypes, referred to as metabotypes, using validated biomarkers and to examine their association with MetS. Materials and Methods: A total of 1245 Korean adults aged 19–79 years were selected from the 2016–2023 Korea National Health and Nutrition Examination Survey. Metabotype risk clusters were derived using k-means clustering based on five biomarkers: body mass index (BMI), uric acid, fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDLc), and non-HDL cholesterol (non-HDLc). Multivariable logistic regression was used to assess associations with MetS. Results: Three distinct metabotype risk clusters (low, intermediate, and high risk) were identified. The high-risk cluster exhibited significantly worse metabolic profiles, including elevated BMI, FBG, HbA1c, triglyceride, and reduced HDLc. The prevalence of MetS increased progressively across metabotype risk clusters (OR: 5.46, 95% CI: 2.89–10.30, p < 0.001). In sex-stratified analyses, the high-risk cluster was strongly associated with MetS in both men (OR: 9.22, 95% CI: 3.49–24.36, p < 0.001) and women (OR: 3.70, 95% CI: 1.56–8.75, p = 0.003), with notable sex-specific differences in lipid profiles, particularly in HDLc. Conclusion: These findings support the utility of metabotyping using routine biomarkers as a tool for early identification of high-risk individuals and the development of personalized prevention strategies in clinical and public health settings. Full article

In healthy humans, insulin at physiological concentrations exerts acute vasodilatory actions on both resistance and terminal arterioles, leading, respectively, to increased total blood flow and the microvascular network volume being perfused. The process of increasing capillary network volume is frequently referred to as “capillary recruitment”. Together these two vascular actions of insulin enhance the delivery of oxygen, nutrients, and insulin itself to tissues. Both processes are diminished by insulin resistance. Here we examined interactions between insulin’s acute (within 2 h) actions on blood pressure (both central and peripheral) and on capillary recruitment in healthy controls and in four distinct groups of people with heightened cardio-metabolic disease (CMD) risk: individuals with obesity, metabolic syndrome, and type 1 or type 2 diabetes. Insulin increased microvascular blood volume (MBV) more effectively in controls than in each of the four CMD risk groups (p < 0.001). Conversely, insulin lowered both central and peripheral systolic pressure (p < 0.05 or less) in each of the CMD risk groups but not in the controls. The insulin-induced blood pressure decrements were greater in the metabolic syndrome, type 2 diabetes, and obesity groups (p < 0.05 or less) than in the controls. The greater blood pressure declines likely reflect decreased sympathetic baroreceptor reflex tone. These effects on blood pressure combined with the diminished dilation of terminal arterioles due to microvascular insulin resistance in the CMD risk subjects led to decreased distal microvascular perfusion as evidenced by changes in MBV. These findings highlight the complex interplay between insulin’s actions on resistance and terminal arterioles in individuals with a high CMD risk, underscoring the importance of addressing microvascular dysfunction in these conditions. Full article

Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial condition associated with significant systemic complications such as cardiovascular disease (CVD), metabolic disorders, muscle wasting, and sarcopenia. While Body Mass Index (BMI) is a well-established indicator of obesity and has prognostic value in COPD, its role in predicting disease outcomes is complex. Muscle wasting is prevalent in COPD patients and exacerbates disease severity, contributing to poor physical performance, reduced quality of life, and increased mortality. Additionally, COPD is linked to metabolic disorders, such as dyslipidemia and diabetes, which contribute to systemic inflammation and worse prognosis and, therefore, should be treated. The systemic inflammatory response plays a central role in the development of sarcopenia. In this review, we highlight the mixed efficacy of statins in managing dyslipidemia in COPD, considering side effects, including muscle toxicity in such a frail population. Alternative lipid-lowering therapies and nutraceuticals, in addition to standard treatment, have the potential to target hypercholesterolemia, which is a coexisting condition present in more than 50% of all COPD patients, without worsening muscle wasting. The interference between adipose tissue and lung, and particularly the potential protective role of adiponectin, an adipocytokine with anti-inflammatory properties, is also reviewed. Respiratory, metabolic and muscular health in COPD is comprehensively assessed. Identifying and managing dyslipidemia and paying attention to other relevant COPD comorbidities, such as sarcopenia and muscle wasting, is important to improve the quality of life and to reduce the clinical burden of COPD patients. Future research should focus on understanding the relationships between these intimate mechanisms to facilitate specific treatment for systemic involvement of COPD. Full article

Background: Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuroplasticity and cognitive development. While exercise has been shown to modulate BDNF levels in adults, evidence in children remains limited and heterogeneous. Methods: A systematic review was conducted following PRISMA guidelines to examine randomized controlled trials investigating exercise effects on BDNF in children aged 5–12 years. The databases searched included FECYT, PubMed, SPORTDiscus, ProQuest Central, SCOPUS, and Cochrane Library through June 2025. Study quality was assessed using the PEDro scale. Results: Five randomized controlled trials (N = 385 participants) met inclusion criteria. Two studies (40%) demonstrated significant BDNF increases following exercise interventions. Successful interventions were characterized by neuromotor activities or martial arts programs, training frequencies ≥ 3 sessions/week, durations ≥ 12 weeks, and healthy participant populations. Methodological quality was mostly fair, with four studies rated as fair and one as good. Conclusions: Structured physical exercise may enhance BDNF levels in healthy children, with neuromotor activities and martial arts showing particular promise. However, children with overweight/obesity may require modified intervention approaches. The evidence supports the implementation of cognitively engaging physical activities in educational settings to optimize brain health during critical developmental periods, though larger standardized trials are needed to strengthen these preliminary findings. Full article

Background and Objectives: Body composition changes with aging and menopause, often leading to increased adiposity and a shift in fat distribution. While BMI is commonly used in clinical practice, it does not accurately reflect fat mass or distribution. This study aims to evaluate age-related changes in both total and regional adiposity using DXA-derived indices in Korean women aged ≥ 40 years and to assess the limitations of BMI-based obesity classification. Materials and Methods: This retrospective multicenter study analyzed the DXA scans and clinical records of 914 Korean women aged 40–80 years who attended menopause clinics across multiple institutions between 2018 and 2021. We analyzed five adiposity indices: body mass index (BMI), total body fat percentage (TB%F), fat mass index (FMI), visceral adipose tissue (VAT) area, and android-to-gynoid (A/G) fat ratio. Excess adiposity was defined as BMI ≥ 23 kg/m², TB%F ≥ 40%, FMI ≥ 9 kg/m², VAT > 100 cm², or A/G ratio > 1.0. Age group comparisons were made using ANOVA, and misclassification was assessed by comparing BMI with other indices. Results: Mean BMI increased with age, peaking in the 60s before declining in the 70s. TB%F and FMI peaked in the 50s, while VAT and A/G ratio increased continuously with age. Excess adiposity was found in 41.9% of women by TB%F, 40.5% by FMI, and 59.4% by VAT in the 70s. Notably, 22% of women with normal BMI (<23 kg/m²) had VAT > 100 cm², and 35.7% had A/G > 1.0, indicating central obesity. Conclusions: DXA-based indices provide a more accurate assessment of adiposity and associated cardiometabolic risks in aging women than BMI alone. Clinical screening strategies should consider incorporating regional fat distribution markers, particularly in midlife and postmenopausal populations, to better identify individuals at risk. Full article

Lipid hormone imbalances involving glucocorticoids, thyroid hormones (THs), and sex hormones have widespread metabolic consequences, contributing to the global increase in obesity and insulin resistance. This review examines the complex role of disrupted lipid hormone pathways in the development of metabolic disorders, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). Endocrine disorders such as hypercortisolism, hypothyroidism, and polycystic ovary syndrome (PCOS) are closely linked to MASLD through shared metabolic pathways. Mechanisms include glucocorticoid-induced gluconeogenesis and lipolysis, impaired lipid clearance in hypothyroidism, and the hyperandrogenism-induced downregulation of hepatic low-density lipoprotein (LDL) receptors. PCOS-related factors—such as central obesity, adipocyte hypertrophy, low adiponectin levels, and genetic predisposition—further promote hepatic steatosis. Thyroid dysfunction may also impair the hepatic deiodination of T4, contributing to lipid accumulation and inflammation. Given the overlapping pathophysiology among endocrine, hepatic, and reproductive disorders, multidisciplinary collaboration is essential to optimize diagnosis, treatment, and long-term cardiometabolic outcomes. Full article

Background/Objectives: Weight gain is frequently observed during and following breast cancer therapy. Women with overweight/obesity have poorer breast cancer prognoses and are more likely to develop comorbidities. The present study describes the development and qualitative assessment of the acceptability of the NutriLife study, a lifestyle weight management intervention with dietetic counseling and digital tools for breast cancer survivors (BCSs). Methods: The intervention was developed using the Medical Research Council (MRC) framework, informed by a systematic literature review and stakeholder input. Acceptability was assessed using the Theoretical Framework of Acceptability (TFA). A total of 22 BCSs with overweight/obesity participated in focus groups, and 5 dietitians/nutritionists specializing in breast cancer in Greece participated in semi-structured interviews. The data were further analyzed using thematic analysis. Results: Stakeholders assessed the intervention as acceptable across all TFA constructs. The intervention was characterized as supportive, easily adaptable, time-efficient, well-organized, beneficial, and professionally driven, with potential barriers including limited personal time, inadequate digital literacy, insufficient self-care, and lack of commitment. Gradually increasing goals may be helpful and less stressful, while educational resources enhance focus on these objectives, thus encouraging intervention participation. Ensuring confidentiality was perceived as central to promoting health. Conclusions: The evidence-based, co-participatory design of the NutriLife intervention was perceived as acceptable by the participating stakeholders and will be pilot-tested in a randomized controlled trial. Full article

Background: The effectiveness of metformin in preventing Type-2 Diabetes Mellitus (T2DM) is examined. There are new available data. Currently, there are no available analyses classifying its effectiveness compared to placebo, standard care, or lifestyle interventions, and there is limited evidence on the combined action of metformin and lifestyle interventions in preventing T2DM. Objective: To calculate the updated overall effectiveness of metformin in preventing T2DM using all available and most recent data, and to explore the effectiveness of metformin and lifestyle interventions in preventing T2DM. Materials and Methods: A search was performed in PubMed and the Cochrane Library Central Register of Controlled Trials (CENTRAL) (from inception to 24 May 2025). A systematic review (SR) and meta-analysis (MA) of randomized controlled trials (RCTs) was carried out, including metformin-naïve adults with any identified diabetes risk factors. The overall effectiveness of metformin was estimated by combining studies that compare metformin against placebo, metformin and standard care against standard care, and metformin plus lifestyle interventions and the same lifestyle interventions. The combined action of metformin and lifestyle interventions was evaluated against standard care. We performed a GRADE assessment of the overall evidence. Results: Overall, metformin may reduce the incidence of T2DM by 23% in high-risk adults (OR 0.77, 95% CI 0.67, 0.88, p-value 0.0001) and 25% in patients with prediabetes (OR 0.75, 95%CI 0.66, 0.86, p-value < 0.0001). It is also effective in both obese and normal-weight patients, in Caucasians, in studies with female predominance, in studies with a mean age over 60 years, at 1700 mg daily, and after 18 months of administration. Effectiveness weakens after interruption of administration. Metformin is more effective compared to placebo and when combined with standard care than standard care alone, but not when combined with lifestyle interventions against lifestyle interventions alone. Metformin and lifestyle interventions reduce the incidence of diabetes in patients with prediabetes by 52% compared to standard care (OR 0.48, 95% CI 0.30, 0.77; p-value 0.002). There are effectiveness concerns in studies with more men than women, Asian Indians and Pakistanis, a mean age below 60 years, 500 mg of metformin daily, and after six months. The effect is reduced during post-intervention. Finally, metformin alone is more effective than standard care (OR 0.56, 95% CI 0.34, 0.90, p-value 0.02). The quality of evidence was moderate for the overall effectiveness of metformin and metformin combined with lifestyle interventions, and low for metformin against standard care. Conclusions: A 1700 mg dose of metformin daily is effective in preventing T2DM, especially in Caucasians, in women over 60 years, in prediabetes, and independent of obesity. Lifestyle interventions and 500 mg of metformin daily may prevent T2DM in patients with prediabetes, especially in men and Asian Indians or Pakistanis under 60 years. The effectiveness of complex interventions is more pronounced than that of metformin alone in patients with prediabetes. Further research is needed for post-intervention effectiveness, patients with any diabetes risk factors, patients from different regions, and women in complex interventions. Full article