To investigate the population-level association between family size and cardiovascular disease (CVD) incidence, focusing on broad patterns rather than causal mechanisms or individual-level effects.

Population level correlations of family size to CVD incidence were analyzed with scatter plots, simple regression, partial correlation and multivariate regression separately. Aging, economic affluence, obesity and urbanization were incorporated in models as potential confounders.

Globally, family size negatively correlated to CVD incidence rate. This relationship remained in partial correlation analyses when controlling for confounders. Stepwise multiple regression revealed that family size may be the most significant predictor of CVD incidence.

Large family size is significantly associated with lower cardiovascular disease (CVD) incidence, potentially due to biological, psychological, and social factors. However, as the data are cross-sectional, this relationship should be interpreted as correlational rather than causal. The association appears more pronounced in developing countries, where contextual factors may amplify its effects.

Herein, we review the devastating consequences of the worldwide obesity epidemic on kidney health and outcomes. We submit that the obesity epidemic is the most pressing public health crisis facing the nephrology community today. A historical approach has been undertaken, wherein major breakthroughs in the recognition and understanding of obesity-related kidney disease (ORKD) are highlighted. We begin with a description of the worldwide obesity epidemic followed by an account of the discovery and characterization of ORKD. A detailed summary of the pathophysiology of ORKD disease is presented, wherein we set forth the following two propositions: first, ORKD is due to a maladaptive response to caloric surplus; and second, this maladaptive response causes kidney damage via hemodynamic (hyperfiltration), hormonal (adipokine dysregulation), and lipotoxic pathways. Each of these pathways is described, with particular emphasis on the relatively recent discovery that the final stage of cellular injury in ORKD is mitochondrial oxidative damage. The prevention and treatment of ORKD are then discussed, including environmental, behavioral, pharmacologic, and surgical options. Finally, we conclude with suggestions for future research to improve early recognition and treatment of ORKD.

This study utilized NHANES data from 2007 to 2018 to investigate the correlation between frailty and the Conicity Index (CI) in individuals aged 60 and above in the United States. The study used NHANES data from 2007 to 2018.CI was calculated as CI = wc / [0.109 × sqrt(bw / Height)]. Frailty was assessed by the frailty index (≥ 0.25). Weighted multivariate logistic regression analysis, subgroup analyses, and interaction tests were used to investigate the connection between CI and the prevalence of frailty. Generalized additive modeling (GAM) was employed to address any non-linear patterns, and the predictive capability of CI for frailty was evaluated by receiver operating characteristic (ROC) analysis. With a 69% rise in the prevalence of frailty for every 0.1 unit increase in the fully adjusted model, the results demonstrated a strong and positive relationship between CI and frailty prevalence (OR: 1.69, 95% CI: 1.53,1.86; P < 0.001). When CI was categorized, the group with the highest CI had a significantly higher prevalence of frailty than the group with the lowest CI (OR = 2.79, 95% CI: 2.22,3.51; P < 0.001). The association between CI and prevalence of frailty was significant in all subgroups. In addition, statistically significant interactions were present in most subgroups. When the CI > reached 1.35, the GAM model demonstrated a threshold effect and a significant nonlinear connection, with a 105% rise in the prevalence of frailty for every 0.1 unit increase in CI. In the male group, CI was a significantly greater indicator of the prevalence of frailty than both BMI and WC. According to this study, frailty in older persons is substantially correlated with a higher CI. Although greater confirmation in large-scale prospective research is required, this study indicates that increased CI is a more reliable predictor of the prevalence of frailty in older men and is significantly linked with its occurrence.

Polycystic Ovary Syndrome (PCOS) is a common health condition related to a woman's hormonal problems. Hormonal imbalance, metabolic disorders, and an increased insulin level mainly characterize the ailment. This detailed review focuses on dietary strategies, macromolecules, macromolecules, and herbal interventions that exception-ally work in PCOS treatment. Research has shown that Mediterranean, low-glycemic index, and ketogenic diets that are modified with individuals in mind are the best ways to resolve insulin resistance, obesity, and lack of ovulation. The other nutrients shown to affect glucose metabolism and play a role in hormone regulation are the macromolecules, such as increased protein and reduced refined carbs. Among the different micronutrients, vitamin D, omega-3 fatty acids, and inositol were shown to be the most vital supplements in the treatment of PCOS-induced oxidative damage, hyperandrogenism, and infertility. Not to mention, cinnamon, curcumin, sage, fennel, and traditional Chinese herbal medicine are among some of the herbal remedies that so far show good potential to be the perfect complementary therapy tools as they create better glycemic control, inflammation reduction, and menstrual cycle regularization. Even though the findings are promising, the current supply of clinical trials for standardizing these nutritional and herbal protocols is lacking. Overall, this report stresses the fact that a customized, holistic diet regime is the best treatment for women with PCOS to make them feel well and live a long and healthy life.

White adipose tissue (WAT) is crucial for whole-body energy homeostasis and plays an important role in metabolic and hormonal regulation. While healthy WAT undergoes controlled expansion and contraction to meet the body's requirements, dysfunctional WAT in conditions like obesity is characterized by excessive tissue expansion, alterations in lipid homeostasis, inflammation, hypoxia, and fibrosis. Obesity is strongly associated with an increased risk of numerous cancers, with obesity-induced WAT dysfunction influencing cancer development through various mechanisms involving both systemic and local interactions between adipose tissue and tumors. Unhealthy obese WAT affects circulating levels of free fatty acids and factors like leptin, adiponectin, and insulin, altering systemic lipid metabolism and inducing inflammation that supports tumor growth. Similar mechanisms are observed locally in an adipose-rich tumor microenvironment (TME), where WAT cells can also trigger extracellular matrix remodeling, thereby enhancing the TME's ability to promote tumor growth. Moreover, tumors reciprocally interact with WAT, creating a bidirectional communication that further enhances tumorigenesis. This review focuses on the complex interplay between obesity, WAT dysfunction, and primary tumor growth, highlighting potential targets for therapeutic intervention.

The main purpose of this study was to assess relationships between absolute and relative handgrip strength (HGS) versus other markers of health (body composition) and physical fitness (VO 2 max, vertical jump) in 220 (112 male) healthy young adults (25±10 years). HGS was measured using a hand dynamometer. Absolute HGS represented the highest grip strength measurement (kg) of the right and left hand combined, while relative HGS represented the absolute HGS divided by body weight (kg/kg). Body composition (lean and fat mass) was measured using dual energy x-ray absorptiometry. VO 2 max was measured using a treadmill peak speed protocol (ml/kg/min), while vertical jump was assessed using a countermovement jump (cm). Absolute HGS (mean=86±22 kg) was positively related with lean mass (r=0.82, p<0.001) and vertical jump (r=0.63, p<0.001), while relative HGS (mean=1.2±0.2 kg/kg) was negatively related with body fat (r=-0.69, p<0.001), but positively correlated with VO 2 max (r=0.47, p<0.001), and vertical jump (r=0.45, p<0.001). Linear models suggest that lean mass, body fat, and vertical jump predicted 69% of variance for absolute HGS (adjusted R 2 =0.71, p<0.001), while lean mass and body fat predicted 49% of variance for relative HGS (adjusted R 2 =0.49, p<0.001). Lower relative HGS scores (<1.0 kg/kg) were associated with higher body fat levels and may represent a quick, simple, marker of health.

Obesity is a metabolic disease that is characterized by an excessive accumulation of adipose tissue (AT) and is often associated with other pathologies. AT is a lipid storage organ with endocrine functions that presents two main phenotypes: white adipose tissue (WAT) and brown adipose tissue (BAT). Preadipocytes or mature white adipocyte cells can differentiate in a middle phenotype with morpho/functional characteristics between WAT and BAT, known as brown-like or beige adipose tissue (BeAT), through the browning process. Considering the interest in stimulating the browning process in metabolic disorders and the lack of clarity, evenness, and reproducibility of the preclinical models, the detailed description of an adipocyte differentiation protocol and the "de novo" development of a beige adipocyte phenotype has been described. Furthermore, the most described stimuli in inducing the browning process, such as PPAR-γ agonists (using rosiglitazone, RGZ) and β-adrenergic stimulators (using isoproterenol, ISO), were evaluated in order to describe their involvement in the browning process and identify a reference compound for the induction of the "de novo" browning.

Immortalized murine embryonic fibroblasts (3T3-L1) cells were differentiated for up to 17 days using a differentiation medium (DM) and a maintenance medium (MM) with or without RGZ or ISO to obtain both the mature white and the beige adipocyte phenotype. The differentiation was evaluated by the Oil Red O (ORO) staining assay, citrate synthase activity, and mitochondrial uncoupling protein 1 (UCP-1) immunodetection and expression performed on different days (T0, T3, T10, and T17) after the induction of differentiation.

The results indicated that RGZ induced morphology and ORO-positive lipid deposits and increased the activity of citrate synthase enzyme and UCP-1 levels overlapping with a beige adipocyte phenotype after 17 days. ISO did not display a significant effect in these experimental conditions.

Overall, this work describes in depth the different phases of the adipocyte differentiation process by offering a detailed and reproducible "de novo" browning differentiation model. Furthermore, the efficacy of the stimulation of the PPAR-γ pathway in obtaining a beige adipocyte phenotype demonstrates that RGZ can induce the browning process and elects it as a perfect reference compound for experimental procedures in this field.

Metabolic score for visceral fat (METS-VF) as an effective marker of visceral obesity has been correlated with non-alcoholic fatty liver disease (NAFLD). This study aims to explore the correlation between METS-VF and both all-cause mortality and cardiovascular disease (CVD)-related mortality among individuals with NAFLD.

A cohort of 6,759 subjects diagnosed with NAFLD was selected from the NHANES during the period from 1999 to 2018. Within this cohort, the prognostic utility of METS-VF for predicting CVD-related and all-cause mortality was assessed.

There was a total of 1254 all-cause deaths (18.6%) and 418 CVD-related deaths (6.2%) at a median follow-up for 9.3 years. Multivariate Cox regression analysis and restricted cubic splines analysis indicated that METS-VF can exhibit a positive non-linearly correlation with CVD mortality (HR: 4.15, 95% CI: 2.31-7.44, p < 0.001) and all-cause mortality (HR: 5.27, 95% CI: 3.75-7.42, p < 0.001), with an identified inflection point at 7.436. Subgroup analyses further revealed a stronger correlation between METS-VF and all-cause mortality among subjects without diabetes. Furthermore, the areas under the curve (AUC) for 1-, 3-, 5-, and 10-year survival rates were 0.756, 0.740, 0.747 and 0.746 for all-cause mortality, and 0.774, 0.751, 0.746 and 0.758 for CVD mortality, respectively, which performs better than the other obesity and IR related index.

Elevated METS-VF independently contributes to an increased risk of both all-cause and CVD mortality in individuals with NAFLD.

Not applicable.

Obesity, characterized by the excessive accumulation of white adipose tissue, is a significant global health burden and a major risk factor for a range of diseases, including malignancies and metabolic disorders. Individuals with high visceral fat content are particularly susceptible to severe complications such as type 2 diabetes, cardiovascular diseases, and liver disorders. However, the pathogenesis of obesity-related metabolic diseases extends beyond simple adiposity. Chronic obesity triggers a prolonged inflammatory response, which leads to tissue fibrosis and sustained organ damage, contributing to multi-organ dysfunction. This review explores the autoimmune mechanisms and inflammatory pathways underlying obesity-induced type 2 diabetes, atherosclerosis, and non-alcoholic fatty liver disease, with an emphasis on their interrelated pathophysiology and the potential for therapeutic interventions.

Childhood obesity is a global health problem, with its prevalence having tripled since 1975. The increase in its prevalence has been predominantly in developing countries, but also in those with high economic status. Nowadays, there are multiple obesity definitions, however, one of the most accurate is the one which defines obesity as the accumulation of excessive body adiposity and not as an body weight excess. Nevertheless, the body mass index (BMI) is the most frequently used tool for its classification, according to the cut-off points established by the Center for Disease Control and World Health Organization tables. In children and adolescents an adiposity excess is related to the appearance of cardiovascular disease in adulthood and with many comorbidities such as metabolic syndrome, insulin resistance, type 2 diabetes, hypertension and metabolic dysfunction-associated steatotic liver disease, among others. Currently, there is still controversy about which is the ideal indicator for measuring overweight and obesity. BMI is still used as a standardized measure but may miss cases in which body composition is pathological despite a BMI within the normal-weight category. An adequate knowledge of the impact on health of dysfunctional adiposity as well as its accurate diagnosis will allow health professionals to address this condition in a more precise and comprehensive manner, and substantially improve the associated cardiometabolic risk and prognosis.

Osteoarthritis (OA) is a chronic joint disease that has long been considered a simple wear-and-tear condition. Over the past decade, research has revealed that various inflammatory features of OA, such as low-grade peripheral inflammation and synovitis, contribute substantially to the pathophysiology of the disease. Technological advances in the past 5 years have revealed a large diversity of innate and adaptive immune cells in the joints, particularly in the synovium and infrapatellar fat pad. Notably, the presence of synovial lymphoid structures, circulating autoantibodies and alterations in memory T cell and B cell populations have been documented in OA. These data indicate a potential contribution of self-reactivity to the disease pathogenesis, blurring the often narrow and inaccurate line between chronic inflammatory and autoimmune diseases. The diverse immune changes associated with OA pathogenesis can vary across disease phenotypes, and a better characterization of their underlying molecular endotypes will be key to stratifying patients, designing novel therapeutic approaches and ultimately ameliorating treatment allocation. Furthermore, examining both articular and systemic alterations, including changes in the gut-joint axis and microbial dysbiosis, could open up novel avenues for OA management.

Cardiometabolic Syndrome (CMS) is associated with increased risks of cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality. The Weight-Adjusted Waist Circumference Index (WWI) has emerged as a novel metric for assessing obesity and its health implications. To investigate the relationship between WWI and mortality in CMS patients, considering the mediating role of inflammatory markers. The study analyzed the National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2018 and identified 6506 patients with CMS. WWI was calculated as the square root of waist circumference (cm) divided by weight (kg). Mortality data were correlated with the National Death Index (NDI). Cox regression models, adjusted for demographic and clinical covariates, assessed the effect of WWI on all-cause and cause-specific mortality. Finally, the role of inflammatory markers in the relationship between WWI and mortality was explored using mediation analysis. The study observed a positive linear association between WWI and all-cause, cardiovascular, and diabetes-related mortalities among CMS patients. After adjusting for demographic and clinical confounders, WWI remained a significant predictor of mortality. Mediation analysis revealed that inflammatory markers, particularly the neutrophil and systemic immune-inflammation index (SII), significantly mediated the relationship between WWI and all-cause mortality. WWI is an independent predictor of mortality in CMS patients, with inflammation potentially linking obesity to mortality risk. These findings may inform clinical risk assessment and management strategies for CMS.

Fermentable carbohydrates and resulting short-chain fatty acids (SCFAs) received attention via modifying potential on obesity-associated systemic low-grade inflammation. However, their effects on inflammation remain poorly understood. In this study, the anti-inflammatory properties of pectin or inulin supplementation were investigated in an atherogenic-fed pig obesity model. Pigs were divided into three atherogenic-fed groups with or without 5% pectin/inulin supplementation (AD, ADp, ADi, n = 10) and a conventional-fed group (CD, n = 10) for a 15-week feeding period. We demonstrated that faecal SCFA concentrations decreased and faecal pH increased in all groups over the feeding period (P < 0.05). SCFA concentrations were comparable between colon and faeces in all groups. Liver inflammatory-marker expressions were on average < 1 in all groups, except TNF-α (AD < CD and ADi; P < 0.01). Inflammatory-marker expressions in abdominal adipose tissue exceeded subcutaneous marker expressions in all groups. AD showed significantly lower IL-1β and CD68 mRNA levels than CD (P < 0.03). Comparing the atherogenic diet groups, the IL-1β mRNA levels were higher in ADi versus AD and ADp (P = 0.02). Our data indicated that fermentable carbohydrates added to an atherogenic diet cannot resolve low-grade adipose tissue inflammatory associated with obesity.

Mitochondria play a central role in nutrient metabolism, besides being responsible for the production of adenosine triphosphate (ATP), the main source of cellular energy. However, the ATP production process is associated with the generation of reactive oxygen species (ROS), which excessive accumulation can cause mitochondrial dysfunction. This dysfunction, in turn, causes the accumulation of fatty acids in the adipose tissue, triggering a local inflammatory process that can evolve into systemic inflammation. In women with obesity, an increase in lipid levels in the placental environment is observed. The high presence of fatty acids compromises the structural integrity and mitochondrial membrane, culminating in the release of ROS. This process damages the DNA of placental cells and causes an inflammatory state, affecting metabolic efficiency. This vicious cycle is characterized by defects in mitochondrial ATP production, which can lead to lipid accumulation and inflammation. In pregnant women with obesity, these mitochondrial changes play a determining role in pregnancy outcomes. Hence, the objective of this study was to search the literature to review the impact of mitochondrial dysfunction in the maternal obesity.

Obesity is a global public health crisis, contributing to chronic disease development and poor prognosis. A large body of evidence consistently demonstrates that increased adiposity leads to many cardiovascular diseases (CVDs) and complications, such as coronary artery disease, heart failure, and arrhythmias, via direct and indirect mechanisms. Therefore, weight management is crucial to reduce and prevent cardiovascular risk. The recent emergence of glucose-like peptide-1 receptor agonists shows remarkable weight reduction and cardiovascular prevention. Despite the clear benefits, controversies and challenges on obesity-related CVD remain. This review aims to provide a comprehensive understanding of obesity-related CVD and explore current remaining tasks.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with an obesity-related phenotype gaining prominence amid the global obesity epidemic. This review explores the distinct pathophysiological mechanisms, diagnostic challenges, and management strategies associated with obesity-induced HFpEF. Obesity contributes to HFpEF through several key mechanisms, including increased blood volume, myocardial hypertrophy and fibrosis, systemic inflammation, and metabolic dysregulation. These factors collectively exacerbate diastolic dysfunction and elevate left ventricular filling pressures, hallmark features of HFpEF. Diagnosing HFpEF in obese patients is particularly challenging due to overlapping comorbidities such as hypertension and diabetes, as well as the reduced reliability of traditional biomarkers such as N-terminal pro-B-type natriuretic peptide. Advanced imaging techniques are crucial in assessing diastolic dysfunction and myocardial remodeling. Managing obesity-related HFpEF requires a comprehensive approach. Lifestyle modifications, including weight loss and exercise, form the cornerstone of treatment, complemented by pharmacological therapies such as sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists. Optimizing comorbidity management is essential, while emerging therapies targeting inflammation, fibrosis, and metabolic dysfunction, alongside precision medicine approaches, offer promising future advancements. This review underscores the need for inclusive clinical trials and personalized treatment strategies to improve outcomes in obesity-related HFpEF. A deeper understanding of this phenotype is crucial for developing targeted interventions that enhance patient care and quality of life. Integrating these insights into clinical practice can help optimize diagnostic accuracy, refine therapeutic approaches, and guide risk stratification for better patient management.

This study aimed to investigate the association between A Body Shape Index (ABSI) and low back pain, with a focus on gender and age differences, using cross-sectional data from the NHANES database.

A total of 14,268 participants were included from four NHANES cycles (1999-2004 and 2009-2010). Low back pain was assessed based on self-reported pain over the past three months, and ABSI was calculated using waist circumference, height, and weight. Multivariate logistic regression models were used to evaluate the association between ABSI and low back pain, adjusting for potential confounders. Restricted cubic spline (RCS) analysis was conducted to assess non-linear relationships, and subgroup analyses were performed based on gender, age and BMI.

Higher ABSI was significantly associated with an increased risk of low back pain (OR for highest quartile = 1.27, 95% CI: 1.07-1.50, p = 0.008). RCS analysis indicated a linear relationship between ABSI and low back pain, with the risk significantly rising when ABSI exceeded 0.85. Subgroup analyses revealed that this association was more pronounced in males (OR = 25.89, 95% CI: 3.11-215.86, p = 0.004) and participants aged ≥ 60 years (OR = 11.11, 95% CI: 2.61-47.26, p = 0.002), while no significant association was observed in females.

The ABSI was associated with low back pain. This association was more prominent in males and older adults. Our findings suggest that ABSI may provide a more nuanced understanding of low back pain risk, particularly in populations with abdominal obesity. Further studies are needed to explore the underlying mechanisms and potential clinical applications of ABSI in low back pain risk assessment.

Obesity, modifiable and an avertable medical condition, has become a global threat due to rapid modernization and industrialization. Swift growth in modernization not only eases the day-to-day life, it also mandates sedentary lifestyle, which leads to various noncommunicable diseases. At present one in eight people in global population are obese, and these booming obese individuals are prone to various other micro- and macrovascular diseases such hyperglycemia, myocardial infraction, hypertension, stroke, and so forth. Ample research had unveiled an intricate association perceived between obesity and Type 2 diabetes mellitus pathogenesis. Although the intake of anti-obesity drugs along with anti-diabetic drugs had effectively regulated the hyperglycemic conditions in diabetic patients, it causes various side effects on long-term usage. Coumarins are phytochemicals that have demonstrated pharmacological properties including anti-inflammatory, antioxidant, anti-tumor, and so forth. In this analysis, we assessed anti-obesity and anti-diabetic potency of aesculetin, a courmarin derivative. The rats were induced obesity with high-fat diet and subjected to streptozotocin infusion to induce hyperglycemia. Obese diabetic induced rats were treated with aesculetin and assessed for its anti-diabetic effect. BMI were assessed in the rats to analyze the anti-obesity effect of aesculetin. Diabetic profile test and lipid profile test were performed to evaluate the anti-diabetic effect of aesculetin. Ameliorative effect of aesculetin in obese rats during hyperglycemic conditions was assessed with renal profile test, hepatic function biomarkers, and by histopathological analysis of cardiac tissue. The anti-inflammatory and antioxidant property were also assessed to determine the mechanism of action of aesculetin. To confirm the anti-obesity potency of aesculetin, adipokines levels were estimated. Aesculetin eminently decreased the BMI, HbA1c, cholesterol levels, and intensified secretion of insulin in obese diabetic rats. It also regulated the renal, hepatic functional markers and prevented cardiac tissue injury in obese diabetic rats. It regulated the adipokines, increased antioxidants, and decreased level of proinflammatory cytokines, thereby prevented obesity-induced hyperglycemic effects in rats. To conclude, our findings had confirmed the supplementary intake of aesculetin prevents obesity-induced hyperglycemic disorder in rats.

Obesity can change the immune microenvironment of adipose tissue and induce inflammation. This study is dedicated to exploring the internal mechanism by which different intensities of exercise reprogram the immune microenvironment of epididymal adipose tissue in nutritionally obese mice. C57BL/6J male obese mouse models were constructed by high-fat diet, which were respectively obese control group (OC), moderate-intensity continuous exercise group (HF-M), high-intensity continuous exercise group (HF-H), and high-intensity intermittent exercise group (HF-T). The exercise group was subjected to aerobic exercise intervention for 8 wk, and samples of mice were collected at the fourth and eighth week, respectively. Mice blood, liver, and adipose tissue of the epididymis were collected for index detection and adipose tissue ordinary transcriptome sequencing. After exercise intervention, when compared with the OC group, the morphology and blood indexes of the exercise groups were significantly improved. The liver lipid content was decreased, adipose tissue inflammation was reduced, and the mRNA and protein expression levels of IL-1β, F4/80, and CD64 in adipose tissue were significantly decreased (P < 0.01). Among the three exercise groups, the effect of the HF-T group was more significant. When compared with the OC group, fibroblast-specific marker genes, neutrophil marker genes, macrophage marker genes, and immune-related signaling pathways were significantly downregulated in the HF-T group. Exercise can reshape the immune microenvironment of adipose tissue, and high-intensity intermittent aerobic exercise is the most effective.NEW & NOTEWORTHY The present study has revealed that obesity is capable of altering the immune microenvironment within adipose tissue, thereby giving rise to inflammation. It has been demonstrated that exercise holds the potential to reverse the onset of inflammatory responses, with high-intensity intermittent aerobic exercise emerging as the most efficacious approach.

Cadmium (Cd) is among the top seven most hazardous environmental contaminants. Minimal risk levels for daily exposure have been established, such as no observable adverse effect level (NOAEL) and lowest observable adverse effect level (LOAEL). Chronic exposure to Cd, at both NOAEL and LOAEL doses, causes toxicity in diverse tissues. However, Cd toxicity in adipose tissue, an endocrine and metabolic organ, remains relatively understudied. We aimed to investigate the potentially toxic effects of chronic Cd exposure (at NOAEL and LOAEL doses) on epidydimal adipose tissue of adult male Wistar rats. Ninety male Wistar rats were divided into three groups (n = 30): Control Cd-free, NOAEL, and LOAEL that received CdCl2 in drinking water for 15 days to 5 months. We evaluated over time zoometry, serum and adipose Cd concentration, redox balance, GLUT4 and Nrf2 expression, histology, leptin, adiponectin, adipose insulin resistance index, free fatty acids, and glucose tolerance. The higher dose group showed a more pronounced and sustained increase in serum and adipose tissue of Cd concentration. Zoometry was similarly affected in both Cd-exposed groups with adipocyte hypertrophy. The redox balance was maintained due to the augmenting of Nrf2 expression. Leptin concentration augmented, while adiponectin diminished. Adipose insulin resistance increased simultaneously to lipolysis and glucose intolerance despite high GLUT4 expression. In conclusion, this study provides strong evidence that chronic Cd exposure, even at minimal risk levels (LOAEL and NOAEL doses), has toxic effects, disrupting the function of epididymal adipose tissue and contributing to metabolic disorders.

The disorders of gut-brain interaction (DGBI) form a heterogeneous group of gastrointestinal disorders that, to date, have no organic basis. The role of oral health in the development of these disorders has not been explored.

The objective of this study was to examine the relationship between oral health and the DGBI.

Data obtained from 166 women with (n = 113) and without fibromyalgia (n = 55) during a prospective observational study conducted in New Zealand during 2022 was evaluated for correlations between oral health measures (WHO oral health questionnaire), and the DGBI (Rome IV survey).

Of the 166 women enrolled in the study, 122 (73.5%) met criteria for at least one DGBI. Women who met criteria for any of the esophageal, gastroduodenal, bowel, and anorectal disorders had significantly lower oral health scores (p < 0.001). For 12 specific DGBI, oral health scores were significantly lower (p < 0.05). Oral health scores were inversely associated with the number of DGBI detected in each participant (ρ = - 0.590, p < 0.001, 95% CI [- 0.69, - 0.48]).

The results of this study suggest there is an association between the oral health and the presence, type, and number of DGBIs in women. Further research to examine the nature of this relationship is required.

The definition of obesity has evolved significantly over the last century, from a simplistic view of excessive eating and laziness to a complex, multifactorial disease with profound health and societal implications. As science progresses, it is essential that we keep improving our knowledge about obesity, taking into consideration, factors like genetics, metabolism, body composition, and the social determinants of health. This article explores how our understanding of this condition has been shaped over the last 100 years considering historical and scientific factors. The history and usefulness of the body mass index (BMI), the development of other anthropometric markers and the evolution in the incorporation of body composition into clinical practice, among other aspects related to the definition of obesity, are discussed. The challenges posed by obesity can be better addressed and more effective strategies for prevention and treatment can be developed adopting a more personalized and holistic approach. Obesity is not only a matter of individual responsibility but a multifaceted public health problem that requires a multidisciplinary and inclusive strategy to address its complexities.

A variety of pathophysiological mechanisms exist by which physical exercise, nutrition, and the microbiome can impact the development of cancer and the response of tumor cells to systemic anti-cancer therapy. Physical exercise positively impacts the different stages of oncological disease and may improve overall survival and quality of life, reduce treatment-associated toxicity, and improve response to immunotherapy. Nutrition impacts quality of life, and novel nutritional regimens and their role in cancer treatment and outcomes are under active investigation. Finally, the microbiome may act as a predictor of response and resistance to immunotherapy. This comprehensive review delves into the interplay between these elements and their impact on oncological outcomes, emphasizing their role in modulating the immune system and enhancing the response to immunotherapy.The data that support the findings of this study are openly available and referenced in the bibliography section.

Background: The study aimed to investigate the association between fat body mass and bone mineral density (BMD) of the lumbar spine (L1-L4), femoral neck, and total body. Methods: We studied 95 patients with Crohn's disease (CD), 68 with ulcerative colitis (UC), and 40 healthy adults (control group-CG) aged 18-50 years old. The BMD of lumbar spine and femoral neck was assessed as well as body composition. Results: A lower fat mass percentage was observed in about 8% of CD, 13% of UC, and 3% of CG. An increased percentage of fat mass was common, and occurred above 50% of CD, 40% of UC, and about 60% of CG. Body fat mass and fat mass percentage were significantly lower among UC compared with the CG (p-value < 0.001) and CD (p-value < 0.01) in women. Body fat mass correlated positively with the BMD and T-score of L1-L4 and total body mass in men with UC. We found a positive correlation between the fat body mass and BMD and T-score of L1-L4, femoral neck, and total body in women with IBD. Among CG, positive correlations occurred between the fat body mass and BMD of L1-L4, BMD of total body, and T-score of total body, but only in men. CRP (C-reactive protein) correlated negatively with fat body mass only in men with CD. Conclusions: A higher fat mass percentage is common among IBD patients and healthy adults despite a normal body mass index. Body fat mass is a predictor of nutritional status and likely influences the course of the disease, as it correlated positively with BMD, T-score, and Z-score. The association between fat tissue and bone health appears to be stronger in women. Further studies are needed to investigate additional factors that may affect bone health in IBD.

Osteoarthritis (OA) affects several joints but tends to be more prevalent in those that are weight-bearing, such as the knees, which are the most heavily loaded joints in the body. The incidence and disability rates of OA have continued to increase and seriously jeopardise the quality of life of middle-aged and older adults. However, OA is more than just a wear and tear disease; its aetiology is complex, and its pathogenesis is poorly understood. Metabolic syndrome (MetS) has emerged as a critical driver of OA development. This condition contributes to the formation of a distinct phenotype, termed metabolic syndrome-associated osteoarthritis (MetS-OA),which differs from other metabolically related diseases by its unique pathophysiological mechanisms and clinical presentation. As key mediators of MetS, metabolic adipokines such as leptin, lipocalin, and resistin regulate inflammation and bone metabolism through distinct or synergistic signaling pathways. Their modulation of inflammatory responses and bone remodeling processes plays a critical role in the pathogenesis and progression of OA. Due to their central role in regulating inflammation and bone remodeling, metabolic adipokines not only deepen our understanding of MetS-OA pathogenesis but also represent promising targets for novel therapeutic strategies that could slow disease progression and improve clinical outcomes in affected patients.

Indole-3-propionic acid (IPA), a metabolite produced by gut microbiota through tryptophan metabolism, has recently been identified as playing a pivotal role in bone metabolism. IPA promotes osteoblast differentiation by upregulating mitochondrial transcription factor A (Tfam), contributing to increased bone density and supporting bone repair. Simultaneously, it inhibits the formation and activity of osteoclasts, reducing bone resorption, possibly through modulation of the nuclear factor-κB (NF-κB) pathway and downregulation of osteoclast-associated factors, thereby maintaining bone structural integrity. Additionally, IPA provides indirect protection to bone health by regulating host immune responses and inflammation via activation of receptors such as the Aryl hydrocarbon Receptor (AhR) and the Pregnane X Receptor (PXR). This review summarizes the roles and signaling pathways of IPA in bone metabolism and its impact on various bone metabolic disorders. Furthermore, we discuss the therapeutic potential and limitations of IPA in treating bone metabolic diseases, aiming to offer novel strategies for clinical management.

Estimated glucose disposal rate (eGDR), is an index of insulin resistance. It is intimately correlated with inflammation and endothelial dysfunction, both of which are contributory factors in the pathogenesis of cardiovascular disease (CVD) and premature mortality. This study aims to explore the correlation between eGDR and both all-cause and CVD-related mortality in adults with metabolic syndrome (MetS).

A total of 8215 subjects with MetS screened from the National Health and Nutrition Examination Survey (NHANES) during the period from 1999 to 2018 were evaluated for the predictive value of eGDR for CVD and all-cause mortality.

Over a median follow-up for 8.3 years, a total of 1537 all-cause deaths (18.7%) and 467 CVD-related deaths (5.7%) were recorded. Logistic regression analyses revealed a significant inverse correlation between eGDR and the risk of having CVD (OR:0.845, 95%CI:0.807-0.884, p < 0.01). Multivariate Cox regression analysis and restricted cubic splines analysis demonstrated that eGDR is non-linearly correlated with both the mortality of CVD (HR: 0.906, 95% CI: 0.850-0.967, p = 0.003) and all-cause mortality (HR: 0.944, 95% CI: 0.912-0.977, p = 0.001), with an identified inflection point at 5.918. Further subgroup analyses indicated a more pronounced correlation between eGDR and all-cause mortality in individuals under 60 years old (HR: 0.893, 95%CI:0.823-0.970) or those with obesity (HR:0.891, 95%CI:0.839-0.946). Mediation analysis revealed that neutrophil to lymphocyte ratio mediated 8.9% of the correlation between eGDR and all-cause mortality.

This study demonstrates, for the first time, that a decrease in eGDR is associated with an increased risk of all-cause and CVD mortality in adults with MetS. The eGDR indices could serve as surrogate biomarkers for monitoring patients with MetS.

The prevalence of obesity and obesity-related clinical conditions, including metabolic-associated steatotic liver disease (MASLD), sarcopenia, and a wide spectrum of pathological manifestations, is rising globally. According to WHO, BMI is the only anthropometric measure currently used to classify obesity, overweight, and underweight. However, emerging research suggests that obesity is a complex pathological state influenced by multiple etiological factors. Given the limitations of BMI, there is a growing need for a more comprehensive assessment of body composition, particularly fat mass quantity and distribution. Bioelectrical impedance analysis (BIA) provides valuable anthropometric data that can help differentiate obesity phenotypes and guide improved therapeutic approaches.

This study aims to analyze body composition using BIA in a randomly selected sample of adults from primary healthcare settings in Bosnia and Herzegovina. The primary goal is to assess total body weight, fat mass quantity, fat distribution, and obesity types prevalent in this population. Additionally, the study seeks to establish reference values for further diagnostic, preventive, and therapeutic strategies to improve public health outcomes.

A cross-sectional study was conducted on adults (≥18 years) in Gračanica, Bosnia & Herzegovina (B6H), from January 2021 to January 2025. Inclusion criteria required participants to provide signed informed consent, while exclusion criteria included acute systemic diseases, severe dehydration, and fasting for more than 24 hours. Anthropometric parameters measured included age, height, weight, BMI, body fat mass (BFM), fat-free mass (FFM), percent body fat (PBF), waist-hip ratio (WHR), and bone mineral content (BMC). Data were analyzed using SPSS (version 18), with results presented as medians, interquartile ranges, and percentiles (5th, 25th, 50th, 75th, and 95th).

A total of 4,628 adults participated in the study, of whom 2,824 (61.0%) were female and 1,804 (39.0%) were male. The median age was 45 years (IQR: 29 years). The findings revealed that over one-quarter of the B&H population is obese, with abdominal obesity being the predominant type. This phenotype is associated with the highest risk for metabolic syndrome and MASLD.

Our study highlights a high prevalence of obesity among the examined individuals in primary care settings in B&H, with abdominal obesity being the most common type. This phenotype is strongly associated with metabolic complications. BIA-derived parameters of fat distribution and visceral fat mass may serve as valuable tools for improving obesity classification and developing more effective preventive and therapeutic strategies.

PIEZO1 has emerged as a mechanoreceptor linked with adipogenesis, adipose tissue (AT) inflammation and insulin resistance. We aimed to determine the impact of obesity and obesity-associated type 2 diabetes (T2D) as well as mechanical compression forces on the expression of PIEZO1 in visceral AT (VAT) and its relation with inflammation.

Blood and VAT samples were obtained from 100 volunteers. Static compression studies in VAT explants were performed to study the PIEZO1 response. The effect of bariatric surgery on the expression of Piezo1 was assessed in a rat model of diet-induced obesity.

Obesity and obesity-associated T2D increased (P < 0.01) gene expression levels of PIEZO1 in VAT mainly due to adipocytes. SWELL1 and key markers of inflammation (NLRP3, NLRP6, IL1B, IL18 and IL8) were also upregulated in VAT in obesity and T2D being significantly associated (P < 0.01) with PIEZO1 levels. We further showed that the static compression of VAT explants promoted an upregulation of PIEZO1 (P < 0.01) and SWELL1 (P < 0.01) expression levels together with a strong increase in the expression and release of key inflammatory mediators. The treatment of THP-1-derived macrophages with the secretome of adipocytes from patients with obesity upregulated (P < 0.001) PIEZO1 levels. Rats undergoing bariatric surgery exhibited decreased (P < 0.01) expression levels of Piezo1 in the epididymal AT.

Static compression triggered an upregulation of PIEZO1 in VAT explants together with a strong inflammation. In addition, the increased expression of PIEZO1 in VAT in obesity and obesity-associated T2D, primarily attributable to adipocytes, is closely associated with SWELL1 and inflammatory markers.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities, including visceral obesity, dyslipidemia, and insulin resistance. In this regard, visceral white adipose tissue (vWAT) plays a critical role, influencing energy metabolism, immunomodulation, and oxidative stress. Adipose-derived stem cells (ADSCs) are key players in these processes within vWAT. While second-generation antipsychotics (SGAs) have significantly improved treatments for mental health disorders, their chronic use is associated with an increased risk of MetS. In this study, we explored the impact of SGAs on ADSCs to better understand their role in MetS and identify potential therapeutic targets. Our findings reveal that olanzapine disrupts lipid droplet formation during adipogenic differentiation, impairing insulin receptor endocytosis, turnover, and signaling. SGAs also alter the endolysosomal compartment, leading to acidic vesicle accumulation and increased lysosomal biogenesis through TFEB activation. PKCζ is crucial for the SGA-induced nuclear translocation of TFEB and acidic vesicle formation. Notably, inhibiting PKCζ restored insulin receptor tyrosine phosphorylation, normalized receptor turnover, and improved downstream signaling following olanzapine treatment. This activation of PKCζ by olanzapine is driven by increased phosphatidic acid synthesis via phospholipase D (PLD), following G protein-coupled receptor (GPCR) signaling activation. Overall, olanzapine and clozapine disrupt endolysosomal homeostasis and insulin signaling in a PKCζ-dependent manner. These findings highlight SGAs as valuable tools for uncovering cellular dysfunction in vWAT during MetS and may guide the development of new therapeutic strategies to mitigate the metabolic side effects of these drugs.

Bidirectional communication between the central nervous system (CNS) and peripheral organs and tissue has been widely documented in physiological and pathological conditions. This communication relies on the bilateral transmission of signaling molecules and substances that circulate throughout the body and reach their target site(s) via the blood and other biological fluids (e.g., the cerebrospinal fluid, the lymph). One of the mechanisms by which these molecular messengers are exchanged is through the secretion of extracellular vesicles (EVs). EVs are known to mediate cell-to-cell communication by delivering biological molecules, including nucleic acids, proteins, lipids, and various other bioactive regulators. Moreover, EVs can cross the blood-brain barrier (BBB), enabling direct communication between the periphery and the brain. In particular, the delivery of microRNAs (miRNAs) can modulate the expression profiles of recipient cells, thereby influencing their functions. This review synthesizes current findings about the brain-periphery cross-talk mediated by EVs-delivered miRNAs. Although this mechanism has been definitively shown in a few cases, much evidence indirectly indicates that it could mediate brain-peripherical organs/tissue communication, especially in pathological conditions. Therefore, understanding this process could provide valuable insights for the treatment and management of neurological and systemic diseases.

Subcutaneous adipose tissue (SAT) is the deepest component of the three-layered cutaneous integument. While mesenteric adipose tissue-based immune processes have gained recognition in the context of the metabolic syndrome, SAT has been traditionally considered primarily for energy storage, with less attention to its immune functions. SAT harbors a reservoir of immune and stromal cells that significantly impact metabolic and immunologic processes not only in the skin, but even on a systemic level. These processes include wound healing, cutaneous and systemic infections, immunometabolic, and autoimmune diseases, inflammatory skin diseases, as well as neoplastic conditions. A better understanding of SAT immune functions in different processes, could open avenues for novel therapeutic interventions. Targeting SAT may not only address SAT-specific diseases but also offer potential treatments for cutaneous or even systemic conditions. This review aims to provide a comprehensive overview on SAT's structure and functions, highlight recent advancements in understanding its role in both homeostatic and pathological conditions within and beyond the skin, and discuss the main questions for future research in the field.

Our study aimed to evaluate the association between the metabolic score for visceral fat (METS-VF) and mortality.

We conducted a cohort study comprising 11,120 participants. We employed weighted multivariable Cox regression analysis to assess the relationship between METS-VF and mortality. Restricted cubic spline analyses were used to investigate potential non-linear associations. Receiver operating characteristic curves were used to evaluate the predictive value of METS-VF and other obesity-related indicators for mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of the results. Mendelian randomization analysis was utilized to assess potential causality.

Over a median follow-up duration of 83 months, a total of 1014 all-cause deaths, 301 cardiovascular deaths, and 262 cancer deaths occurred. For every 0.2-unit increase in METS-VF, the hazard ratios(HRs) of all-cause mortality, cardiovascular mortality, and cancer mortality were 1.13 [95% confidence interval (CI): 1.06, 1.20], 1.18 (95% CI: 1.06, 1.31), and 1.13 (95% CI: 1.03, 1.25), respectively. In addition, restricted cubic spline analyses revealed no significant non-linear associations between METS-VF and all-cause mortality, cardiovascular mortality, and cancer mortality. In multivariate Cox regression models, hazard ratios of all-cause mortality, cardiovascular mortality and cancer mortality were higher in the highest METS-VF group compared to the reference group. Subgroup and sensitivity analyses confirmed that our results were robust. Receiver operating characteristic curves indicated that METS-VF predicted mortality better than other obesity-related indicators. Mendelian randomization analysis confirmed significant causal relationships.

METS-VF was positively associated with all-cause mortality, cardiovascular mortality, and cancer mortality. These findings suggest that METS-VF could serve as a straightforward, reliable, and cost-effective marker for identifying individuals at high risk of mortality.

Obesity and aging are associated with the progressive loss of brown adipose tissue (BAT), an increase in visceral white adipose tissue (vWAT), and a reduction in subcutaneous white adipose tissue (sWAT). The progressive expansion of visceral obesity promotes a low grade of systemic chronic inflammation (meta-inflammation), contributing to the onset of comorbidities such as type 2 diabetes mellitus (T2DM), metabolic syndrome, and even cancer. Thus, preserving the thermogenic activity of adipose tissue and improving the metabolic flexibility of sWAT could be an effective strategy to prevent the development of metabolic chronic diseases and promote healthy aging. Precision nutrition has emerged as a complementary approach to control the metabolic alterations associated with unhealthy obesity and aging. In a previous work, we described that a silymarin-enriched extract from milk thistle (Mthistle) increased markers of browning and thermogenesis in vitro in human differentiated adipocytes (SGBS).

Therefore, this study aims to evaluate the potential of Mthistle to activate thermogenesis in a preclinical model of high-fat diet (HFD)-induced obesity (DIO).

Our results demonstrate that Mthistle increases systemic energy expenditure (EE), preserves body temperature after cold exposure, improves insulin resistance, and reduces inflammatory markers in WAT.

Based on these results, silymarin-enriched extract from Mthistle may be proposed as a nutraceutical for the management of metabolic chronic diseases and/or accelerated aging.

Background/Objectives: Prostate cancer is the second leading cause of cancer death among American men, following lung cancer. While diet and exercise have been extensively studied in relation to prostate cancer prevention, the evidence remains inconclusive. Methods: A comprehensive literature search was performed to identify observational studies investigating the association between ultra-processed food (UPF) consumption and prostate cancer risk and mortality, determined by the NOVA classification system. In addition, we conducted subgroup analyses to assess the association based on study design, age, and data collection methods. Results: Six studies were identified, including four cohort studies and two case-control studies. No significant association was found between high UPF consumption and increased risk of prostate cancer [RR = 1.02, 95% confidence interval (CI) = 0.96-1.08, n = 5]. However, there was a slight increase in mortality (RR = 1.15, 95% CI = 0.99-1.35, n = 2). A subgroup analysis by the dietary assessment method revealed an RR of 1.01 (95% CI = 0.93-1.09) for studies using the food frequency questionnaire (FFQ) and 1.04 (95% CI = 0.93-1.16) for studies using 24-h recalls. There was no significant heterogeneity among the studies (I2 = 0, p = 0.82). Conclusions: This meta-analysis suggests no significant association between high UPF consumption and prostate cancer risk. Given the known associations with other chronic diseases, the potential public health implications of reducing UPF consumption remain important. Further research with the use of more robust food assignment systems and more precise dietary assessments is needed to clarify the role of UPF in prostate cancer development.

Vitiligo is a commonly acquired pigmentary disease characterized by the progressive destruction of melanocytes. The role of adipose tissue in vitiligo remains unclear. To investigate the role of adipose tissue in the pathogenesis of vitiligo, 50 patients newly diagnosed with vitiligo and 40 age- and sex-matched healthy controls were enrolled, and fat mass and distribution using dual-energy X-ray absorptiometry (DXA) and serum adipokine levels using enzyme-linked immunosorbent assay were assessed. The trunk and whole-body fat mass and the trunk/limb fat mass ratio were significantly higher in patients with vitiligo. Higher leptin and resistin levels and lower adiponectin levels were observed. Positive correlation of the trunk fat mass index with vitiligo area scoring index scores (r = 0.38, p = 0.0071) was found. Additionally, plasma adiponectin levels were negatively correlated with vitiligo disease activity scores (r = -0.307, p < 0.05). Receiver operating characteristic curve analysis showed that the percentage of limb lean tissue mass, trunk/limb fat mass ratio, and serum adipokine levels achieved a high area under the curve score for distinguishing patients with vitiligo from healthy controls. In conclusion, the incidence of central obesity and adipokine dysregulation was higher in patients with vitiligo. The potential role of adipose tissue in the pathogenesis of vitiligo should be emphasized.

Objective: Adult growth hormone deficiency (AGHD) is characterized by central adiposity and metabolic disorders. Asprosin, a newly discovered adipokine, plays a crucial role in connecting adipose tissue function with the development of metabolic syndrome. This study aims to evaluate the circulating levels of asprosin in AGHD patients and explore the potential correlation between asprosin levels and various metabolic parameters. Subjects and Methods: Forty male patients with AGHD (mean age: 33.5 ± 9.5 yrs and mean BMI: 25.0 ± 4.5 kg/m2) and forty age-, gender-, and BMI-matched non-AGHD controls were enrolled. Medical history, anthropometric parameters (weight, height, waist circumference), and biochemical and hormonal investigations were collected from the electronic medical record system. Fat mass, fat percentage, and fat-free mass (FFM) were evaluated by bioelectrical impedance. Serum levels of asprosin were measured by ELISA. Results: Patients with AGHD demonstrated notably increased waist-to-hip ratios, triglyceride levels, and decreased HDL-cholesterol levels compared with the control group. In additionally, AGHD patients exhibited significantly higher serum levels of asprosin compared with controls (p=0.039). A notable association was observed between serum asprosin levels and FFM, triglycerides, and HDL-cholesterol levels in the whole population. Conclusions: Our study highlights distinct metabolic alterations in AGHD patients when matched for BMI with controls and investigates variations in serum asprosin levels for the first time. These findings have significant implications for identifying potential biomarkers for metabolic syndrome risk in AGHD patients and informing future treatment approaches.

Background: Chronic venous disease (CVD) represents a significant health challenge, particularly in obese individuals. This study focuses on the interplay between inflammation, obesity, and CVD, by analyzing the role of inflammatory markers in the disease progression. Methods: Clinical and paraclinical data of 619 patients hospitalized and treated in the Phlebology Department (1stSurgical Department, "Pius Brînzeu" Emergency County Hospital Timișoara, Romania) between 2018 and 2024 were analyzed. Results: The statistical analysis revealed that age, C-reactive protein (CRP), fibrinogen, and absolute neutrophil count (ANC) were key predictors of CVD progression. Specifically, elevated CRP and fibrinogen levels correlated strongly with increased CVD severity, particularly in patients with higher body-mass index (BMI). BMI, while not an independent predictor, contributed indirectly to the disease severity through its association with these inflammatory markers. The logistic regression model incorporating age, BMI, CRP, fibrinogen, and ANC demonstrated a high predictive accuracy, with an area under the curve (AUC) of 0.902, highlighting the models reliability in stratifying patients at risk for severe CVD. Conclusions: This predictive model not only aids in identifying high-risk patients but also reinforces inflammation as a critical therapeutic target in CVD management.