Search Results (86)

Background: The gut microbiota is increasingly recognized as a key modulator in obesity management, influencing host energy balance, lipid metabolism, and inflammatory pathways. With obesity prevalence continuing to rise globally, dietary interventions that promote beneficial microbial shifts are essential for enhancing weight loss outcomes and long-term health. Objective: This study investigated the effects of the multicomponent Weight Loss Maintenance 3 Phases Program (WLM3P), which integrates caloric restriction, a high-protein low-carbohydrate diet, time-restricted eating (10h TRE), dietary supplementation (prebiotics and phytochemicals), and digital app-based support on gut microbiota composition compared to a standard low-carbohydrate diet (LCD) in adults with obesity. The analysis focused exclusively on the 6-month weight loss period corresponding to Phases 1 and 2 of the WLM3P intervention. Methods: In this sub-analysis of a randomized controlled trial (ClinicalTrials.gov Identifier: NCT04192357), 58 adults with obesity (BMI 30.0–39.9 kg/m²) were randomized to the WLM3P (n = 29) or LCD (n = 29) groups. Stool samples were collected at baseline and 6 months for 16S rRNA sequencing. Alpha and beta diversity were assessed, and genus-level differential abundance was determined using EdgeR and LEfSe. Associations between microbial taxa and clinical outcomes were evaluated using regression models. Results: After 6-month, the WLM3P group showed a significant increase in alpha diversity (p = 0.03) and a significant change in beta diversity (p < 0.01), while no significant changes were observed in the LCD group. Differential abundance analysis revealed specific microbial signatures in WLM3P participants, including increased levels of Faecalibacterium. Notably, higher Faecalibacterium abundance was associated with greater reductions in fat mass (kg, %) and visceral adiposity (cm²) in the WLM3P group compared to LCD (p < 0.01). Conclusions: These findings suggest a potential microbiota-mediated mechanism in weight loss, where Faecalibacterium may enhance fat reduction effectiveness in the context of the WLM3P intervention. Full article

In placental mammals, the co-option of vertebrate orthologous ATP1B4 genes has profoundly altered the properties of the encoded BetaM proteins, which function as bona fide β-subunits of Na,K-ATPases in lower vertebrates. Eutherian BetaM acquired an extended Glu-rich N-terminal domain resulting in the complete loss of its ancestral function and became a skeletal and cardiac muscle-specific component of the inner nuclear membrane. BetaM is expressed at the highest level during perinatal development and is implicated in gene regulation. Here we report the long-term consequences of Atp1b4 ablation on metabolic parameters in adult mice. Male BetaM-deficient (Atp1b4−/Y) mice have remarkably lower body weight and adiposity than their wild-type littermates, despite higher food intake. Indirect calorimetry shows higher energy expenditure (heat production and oxygen consumption) with a greater spontaneous locomotor activity in Atp1b4−/Y males. Their lower respiratory exchange ratio suggests a greater reliance on fat metabolism compared to their wild-type counterparts. Consistently, Atp1b4−/Y KO mice exhibit enhanced β-oxidation in skeletal muscle, along with improved glucose and insulin tolerance. These robust metabolic changes induced by Atp1b4 disruption demonstrate that eutherian BetaM plays an important role in regulating adult mouse metabolism. This demonstrates that bypassing the co-option of Atp1b4 potentially reduces susceptibility to obesity. Thus, Atp1b4 ablation leading to the loss of evolutionarily acquired BetaM functions serves as a model for a potential alternative pathway in mammalian evolution. Full article

Objectives: This study aims to assess the clinical efficacy of micro-fragmented adipose tissue (MFAT) therapy over three years in patients with KOA and to determine whether short-term improvements at three months can forecast long-term outcomes. Methods: A retrospective, observational study was conducted on 335 patients diagnosed with KOA who received a single MFAT injection. The patients were followed up at 3 months, 6 months, 1 year, 2 years, and 3 years, with assessments using the Visual Analog Scale (VAS), Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS). Statistical analysis was performed to assess the differences in preoperative and postoperative scores (VAS, OKS, WOMAC, KOOS) to evaluate the predictive role of 3-month score changes on long-term clinical outcomes. Results: All measured scores (VAS, OKS, WOMAC, KOOS) showed significant improvement at 3 months, with sustained improvements through 3 years (p < 0.001). Early score changes at 3 months were significantly associated with improved clinical outcomes at 1, 2, and 3 years (p < 0.05). Logistic regression confirmed early post-treatment improvements as independent predictors of long-term benefit, except for the VAS score at 3 years (p = 0.098). A comparative analysis between completers and dropouts showed no baseline differences; however, significant outcome differences emerged at later follow-up points. Due to insufficient data at the 3-year mark among dropouts, statistical comparisons were not possible for that time point. Conclusions: MFAT treatment was associated with consistent symptomatic improvement in patients with KOA, and early clinical response at 3 months served as a reliable predictor of long-term pain and function outcomes. While this study focused on patient-reported symptom relief and not structural regeneration, the results support MFAT as a minimally invasive option for symptom management. Early post-treatment response may serve as a useful tool for clinicians to predict long-term therapeutic success and personalize treatment strategies for KOA patients. Full article

Background/Objectives: Metabolic syndrome is one of the leading causes of mortality worldwide, with high-fat diet (HFD) intake being a significant driving force. Despite long-term research, new interventions are still being sought to improve cardiovascular disorders associated with metabolic syndrome. Methods: To explore the therapeutic potential of a slow-releasing H₂S donor, we evaluated the effects of 3 weeks of treatment with GYY-4137 on systolic blood pressure (sBP), cardiac parameters, adiposity, selected plasma markers, and the vascular function of the thoracic aortas (TAs) and mesenteric arteries (MAs) isolated from male spontaneously hypertensive rats (SHRs) fed an HFD for 8 weeks. Results: HFD administration induced cardiac remodeling, increased adiposity, and decreased adrenergic contractility in both TAs and MAs. Moreover, although high-fat intake improved TAs relaxation, it decreased aortic protein expression of endothelial NO synthase and the involvement of NO in vasoactive responses of both TAs and MAs. In addition, protein expression of inducible NOS and tumor necrosis factor alpha (TNFα) in aortas was increased, as were plasma levels of chemerin, which has been proposed as a possible link among metabolic and vascular disorders and inflammation. Treatment with GYY-4137 reduced sBP, improved relaxation of the MAs, partially restored the contractility of the TAs, generally restored NO signaling, and decreased the protein expression of the inducible NOS and TNFα, as well as plasma chemerin levels. Conclusions: A slow H₂S-releasing donor could partially ameliorate the metabolic changes induced by increased fat intake during essential hypertension and trigger beneficial vasoactive effects associated with the NO signaling restoration and suppression of inflammation. Full article

Adipocyte hypertrophy in individuals with obesity is connected to alterations in adipocyte function. These pathophysiological changes are studied using animal models and adipose tissue engineering. However, knockdown, overexpression, and stimulation studies would benefit from an easily applicable cell model. Although several models (free fatty acids, glucose restriction, and long-term incubation) have previously been described, our evaluation demonstrated that they lack important features described for hypertrophic adipocytes found in obesity. Therefore, we aimed to develop a cell model depicting the pathophysiological state of adipocytes in obesity by applying novel approaches (insulin, macrophage supernatant, and Tnfα) using 3T3-L1 cells. To analyze changes in adipocyte phenotype and function, we detected the cell size, lipid accumulation, insulin sensitivity, cytokine/adipokine secretion, and expression of lipolytic enzymes. Combining long-term incubation with insulin and Tnfα co-stimulation, we found significantly increased cell size and lipid accumulation compared to 3T3-L1 adipocytes differentiated with standard protocols. Furthermore, these adipocytes showed significantly reduced insulin sensitivity, adiponectin secretion, and lipolytic enzyme expression, accompanied by increased IL6 and leptin secretion. In summary, the described cell model depicts pathophysiologically hypertrophic 3T3-L1 adipocytes. This model can be used for knockdown, overexpression, and stimulation studies, thereby serving as an alternative to primary cells isolated from DIO mice. Full article

Background: Low-dose antibiotic contamination in animal feed is a persistent global food safety challenge. Transient early-life exposure to low-dose penicillin (LDP) is known to induce metabolic syndrome (MetS) in adult mice, but the underlying mechanisms are unclear. Introduction: This study investigated the role of gut microbiota (GM) and intestinal immunity in mediating the long-term metabolic effects of early-life LDP exposure. Methods: Mice were exposed to LDP transiently during early life. GM composition was analyzed. Intestinal IgA responses were quantified. Bacterial encroachment, systemic and adipose tissue inflammation, and diet-induced MetS were assessed. Germ-free (GF) mice received GM transplants from LDP-exposed or control mice to test causality and persistence. Results: Early-life LDP exposure significantly disrupted GM composition, particularly in the ileum, in 30-day-old mice. These GM alterations caused persistent suppression of intestinal IgA responses, evidenced by reduced IgA-producing cells and sIgA levels. This suppression was constrained to early-life exposure: transferring LDP-modified GM to GF mice produced only a transient reduction in fecal sIgA. The LDP-induced sIgA reduction decreased IgA binding of bacteria, leading to increased bacterial encroachment and systemic and adipose tissue inflammation. These pathological changes exacerbated diet-induced MetS. Discussion: Our findings demonstrate that early-life LDP exposure induces persistent intestinal IgA deficiency through lasting GM alterations initiated in early development. This deficiency drives bacterial encroachment, inflammation, and ultimately exacerbates MetS. Conclusions: The exacerbation of diet-induced metabolic syndrome by early-life LDP exposure occurs through an intestinal sIgA-dependent pathway triggered by persistent GM disruption. This highlights a critical mechanism linking early-life antibiotic exposure, gut immune dysfunction, and long-term metabolic health, with significant implications for food safety. Full article

Lipedema is a chronic disease of the subcutaneous adipose tissue that mostly affects women. The etiopathogenesis of the disease is still poorly understood. Lipedema typically develops after major hormonal changes, such as puberty, pregnancy, and menopause. Alongside genetic susceptibility, the pathophysiological mechanism involving hormonal changes is mostly linked to aberrantly expressed estrogen receptors in adipose tissue. Lipedema has no known cure, and current therapies aim primarily to reduce symptoms, avoid complications, and slow the disease progression. Achieving or maintaining a healthy body composition, preserving or regaining mobility and functionality, preventing the progression of disease, and reducing pain and other symptoms are all possible outcomes of proper nutrition and weight management. Since nutrition may provide a long-term solution to control almost constant inflammation, it should be a major part of lipedema treatment. Despite the lack of a specific, scientifically supported diet for lipedema patients, several dietary approaches have been suggested. In this comprehensive narrative review, supported by published revisions and peer-reviewed studies following scrutiny of digital medical databases, the current state of knowledge and theories regarding the hormonal etiopathogenesis of lipedema are presented, as well as the role of nutritional intervention in reducing its symptoms and progression. Full article

Background and objective: Studies using metabolomics to study bariatric surgery have shown that amino acids are one of the most changed groups of metabolites after the intervention. However, the surgery-related variation in individual amino acids, as well as the long-term impact and the differences between the types of surgeries, have been poorly studied. The aim of this study was to investigate the changes in circulating amino acids after three types of bariatric surgery up to 36 months after the intervention. Methods: We studied 63 participants diagnosed with T2D at baseline, who received either a sleeve gastrectomy, a Roux-en-Y gastric bypass or a biliopancreatic diversion with duodenal switch. We measured the concentrations of 16 circulating amino acids in fasting plasma before the surgery as well as after 4, 12, 24 and 36 months via liquid chromatography coupled with mass spectrometry (LC-MS/MS). Results: Eleven circulating amino acids were significantly modified by bariatric surgery. Glutamate, leucine and isoleucine showed the greatest decrease. Most of the changes in circulating amino acids occurred within 1 year of the operations. Only one measured plasmatic amino acid (threonine) had a significantly different change pattern according to surgery types. In repeated-measure correlations, changes in circulating amino acids were significantly associated with changes in adiposity and metabolic markers. Conclusions: Bariatric surgery changes the levels of most circulating amino acids, and the effect occurs in the short term without major differences between surgery types. The mechanisms explaining these changes are not elucidated but likely include modifications in amino acid metabolism. Full article

Pediatric obesity is associated with a wide range of comorbidities beyond metabolic changes, affecting cardiovascular, endocrine, reproductive, musculoskeletal systems, and also mental health. Hypertension, commonly observed in children with obesity, increases the risk of long-term cardiovascular disease. Polycystic ovary syndrome (PCOS) presents another significant endo-reproductive challenge that often develops during adolescence in females, leading to further comorbidities in adulthood. Additionally, excess adiposity can negatively impact bone health by modifying bone metabolism and increasing fracture risk. Obesity is also strongly linked to mental health disorders, including depression, anxiety, and low self-esteem, which can further exacerbate unhealthy lifestyle behaviors and disorders. Given the limitations and poor adherence of traditional treatment strategies, nutraceuticals have emerged as potential complementary therapies due to their bioactive properties. Various compounds have demonstrated antihypertensive, insulin-sensitizing, and anti-inflammatory effects, while others support bone metabolism and promote mental well-being. Herewith, we discuss the role of nutraceuticals in managing hypertension, PCOS, bone health, and mental health issues in individuals with obesity, evaluating their mechanisms of action and clinical relevance. Integrating nutraceutical compounds with dietary and lifestyle interventions may improve treatment outcomes and prevent obesity-related comorbidities. Further, we emphasize the need for further large-scale clinical studies, especially in pediatric patients. Full article

Background/Objectives: Osteoporosis is a major public health concern, due to its high risk of fractures and disability and associated medical costs. Romosozumab, an anabolic agent, has been approved for the treatment of osteoporosis in postmenopausal women at high risk of fractures. However, limited data exist on its long-term effects in the Korean population, particularly regarding its impact on bone mineral density (BMD), bone turnover markers, and body composition. This study aimed to evaluate the 12-month effects of romosozumab treatment on BMD, bone turnover markers, and body composition in postmenopausal Korean women with high-fracture-risk osteoporosis (T-scores ≤ −3.0). Additionally, the impact of concomitant postmenopausal hormone therapy (MHT) on BMD changes was assessed. Methods: This multicenter, retrospective observational study included 50 postmenopausal women diagnosed with osteoporosis (T-scores ≤ −3.0) who received 12 monthly doses of romosozumab (210 mg) at two hospitals in Korea. Changes in BMD in the lumbar spine, femoral neck, and total hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone turnover markers, including procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX), were measured at baseline and at 3, 6, and 12 months. Changes in body composition, including the skeletal muscle index (SMI), body mass index (BMI), and visceral adipose tissue (VAT), were also analyzed. Results: After 12 months of romosozumab treatment, BMD significantly increased at the lumbar spine (14.65%), femoral neck (6.58%), and total hip (4.19%) (p < 0.05). P1NP levels increased significantly at 3 months (+37.9%), but returned to baseline at 6 months, while CTX levels continuously decreased (−27.8%) over 12 months. No significant changes were observed in SMI or BMI, but the VAT showed a slight decreasing trend (p < 0.05). Additionally, patients receiving concomitant MHT demonstrated a significantly greater increase in lumbar spine BMD compared to those receiving romosozumab alone (p < 0.05), while no significant differences were observed in femoral neck and total hip BMD. Conclusions: This study demonstrated that 12 months of romosozumab treatment significantly improved BMD and bone turnover markers in postmenopausal Korean women with severe osteoporosis. The combination of romosozumab and MHT further enhanced lumbar spine BMD gains. These findings support the use of romosozumab as an effective treatment for high-risk osteoporotic fractures in postmenopausal Korean women, and suggest potential benefits of a combined therapeutic approach. Full article

Atrial fibrillation (Afib) recurrence after catheter ablation (CA) remains a significant clinical challenge, driven by a complex and dynamic interplay of structural, electrical, and autonomic mechanisms. While pulmonary vein isolation (PVI) is the cornerstone of CA, recurrence rates remain substantial, highlighting the need to understand the evolving pathophysiology beyond PV reconnection. Post-ablation changes, including inflammation, edema, oxidative stress, and ischemia, create a transient proarrhythmic state that may contribute to early recurrence. Over time, atrial remodeling, fibrosis, and residual autonomic activity further sustain arrhythmogenicity. Additionally, epicardial adipose tissue promotes atrial myopathy, accelerating disease progression, particularly in patients with risk factors such as older age, female sex, obesity, hypertension, obstructive sleep apnea, and heart failure. The multifactorial nature of Afib recurrence underscores the limitations of a “one-size-fits-all” ablation strategy. Instead, a patient-specific approach integrating advanced mapping techniques, multimodal imaging, and computational modeling is essential. Artificial intelligence (AI) and digital twin models hold promise for predicting recurrence by simulating individualized disease progression and optimizing ablation strategies. However, challenges remain regarding the standardization and validation of these novel approaches. A deeper understanding of the dynamic interconnections between the mechanisms driving recurrence is crucial for improving long-term CA outcomes. This review explores the evolving nature of Afib recurrence, emphasizing the need for a precision medicine approach that accounts for the continuous interaction of pathophysiological processes in order to refine patient selection, ablation strategies, and post-procedural management. Full article

Maternal obesity is an escalating public health concern that adversely affects pregnancy outcomes. Adipokines play a key role in regulating metabolism and fetal development, but their dynamic changes during pregnancy remain inadequately understood. Objective: This study investigates maternal and fetal adipokine variations throughout pregnancy and their associations with maternal body mass index (BMI), abdominal wall thickness, and neonatal outcomes. Methods: A prospective case-control study was conducted involving 74 pregnant women categorized by BMI. Maternal blood samples were collected at mid-pregnancy and delivery, and additional analysis of umbilical-cord blood was performed. Clinical parameters such as BMI, abdominal wall thickness, and fetal growth metrics were also recorded. Results: Adiponectin levels were significantly lower in obese pregnancies, whereas leptin and visfatin levels increased with higher maternal BMI. Umbilical-cord blood leptin levels correlated positively with maternal BMI and neonatal birth weight, while ghrelin levels were reduced in neonates born to obese mothers. Significant adipokine fluctuations were observed between mid-pregnancy and delivery. Conclusions: Maternal obesity is associated with distinct alterations in adipokine profiles. These findings highlight the potential of maternal adipokines, given their links to maternal adiposity, as predictive biomarkers for adverse pregnancy outcomes and long-term metabolic risks in offspring. Further interventional research is warranted to evaluate targeted strategies aimed at improving perinatal metabolic health. Full article

Background: Insulin resistance, visceral adiposity, excess body weight, and symptoms of hyperandrogenism often accompanies Polycystic Ovary Syndrome (PCOS). A balanced diet plays a key role in improving the metabolic and biochemical parameters in affected women. This study aims to assess whether dietary improvements in patients with suspected PCOS may affect the severity of the disease and the metabolic and hormonal profile. Methods: The analysis of the relationships between self-declared nutritional changes and biochemical and metabolic parameters included 154 women at the same stage of PCOS diagnosis. Results: Over half of participants reported dietary modifications. Women reducing sweets, fatty red meat, and alcohol intake for >6 months had significantly lower total testosterone (TT) levels compared to those who did not (p < 0.05). Mean TT levels were: 0.375 ± 0.18 ng/mL (median 0.340) vs. 0.787 ± 2.19 ng/mL (median 0.390) for red meat (p = 0.008), 0.359 ± 0.18 ng/mL (median 0.335) vs. 0.681 ± 1.9 ng/mL (median 0.4) for sweets (p = 0.02), and 0.388 ± 0.19 ng/mL (median 0.34) vs. 0.917 ± 2.65 ng/mL (median 0.425) for alcohol (p = 0.004). Patients with dietary changes in the past 6 months had higher androgen levels, BMI, systolic blood pressure and triglycerides than patients with long-term dietary changes (p < 0.05). There were no statistically significant differences in key metabolic and biochemical parameters when comparing self-reported diets based on glycemic index (low vs. high). Conclusions: A healthy, balanced diet for women with PCOS requires a multifaceted approach with clear, defined goals. This leads to better results than broad, general dietary recommendations. Long-term dietary changes improve biochemical and metabolic parameters, but maintaining these benefits requires continuous patient motivation. Full article

Background/Objectives: This study investigates the effects of a high-fat diet (HFD) during pregnancy and lactation on maternal and offspring health, focusing on behavioral, metabolic, and fatty acid composition outcomes in a rat model. Methods: Twelve female Sprague–Dawley rats were fed either a control diet, CD (n = 6), or HFD (n = 6) for 12 weeks, encompassing mating, gestation, and lactation periods (18 weeks). Anxiety-like behavior, maternal behavior, depression-like behavior, and social play were studied. Post mortem, the liver function, hepatic steatosis, and fatty acid composition (erythrocytes, liver, adipose tissue) were evaluated. In regard to desaturase enzymes (Δ-6D and Δ-5D), liver activity, protein mass, and gene expression (RT-PCR) were analyzed. Additionally, gene expression of PPAR-α, ACOX, CPT1-α, SREBP-1c, ACC, and FAS was assessed. Statistical analysis was performed using Student’s t-test, mean ± SD (p < 0.05). Results: The HFD significantly increased maternal weight and anxiety-like behavior while reducing social interactions exclusively in male offspring (p < 0.05). It also led to a significant decrease in the synthesis and content of n-3 PUFAs in the analyzed tissues, induced hepatic steatosis, and upregulated the expression of pro-lipogenic genes in the maternal liver. Conclusions: These findings suggest that long-term HFD consumption alters tissue fatty acid composition, disrupts metabolic homeostasis, and contributes to behavioral changes, increasing anxiety-like behaviors in pregnant dams and reducing social interactions in male offspring. Overall, this study provides further insight into the detrimental effects of HFD consumption during the perinatal period. Full article

Understanding mesenchymal stem cell (MSC) behavior on glycated collagen is crucial for advancing regenerative medicine and understanding pathological mechanisms in diseases such as diabetes, cancer, and aging. While previous research has demonstrated reduced MSC interaction with glycated collagen under static conditions due to disrupted integrin signaling, these studies did not accurately replicate the dynamic mechanical environment that MSCs encounter in vivo. Here we present a comprehensive investigation comparing adipose-derived MSC (ADMSC) behavior under both dynamic flow conditions and static adhesion, revealing unexpected temporal dynamics and challenging existing paradigms of cell–matrix interactions. Using a sophisticated microfluidic BioFlux system combined with traditional static adhesion assays, we examined ADMSC interactions with native collagen for 1-day glycated (GL1), and 5-day glycated (GL5) samples. Under flow conditions, MSCs demonstrated remarkably rapid attachment—within 3–5 min—contrasting sharply with the classical 2 h static incubation protocol. This rapid adhesion was particularly enhanced on 5-day glycated collagen, though subsequent testing revealed significantly weaker adhesion strength under shear stress compared to native collagen. Static conditions also showed a distinct pattern: increased ADMSC adhesion to glycated samples within the first 30 min, followed by a progressive decrease in adhesion and compromised cell spreading over longer periods. Atomic force microscopy (AFM) analysis revealed significant changes in collagen surface properties upon glycation. These included a substantial reduction in the negative surface charge (from ~800 to 600 mV), altered surface roughness patterns (Rrms varying from 3.0 ± 0.4 nm in native collagen to 7.70 ± 0.6 nm in GL5), and decreased elasticity (Young’s modulus dropping from 34.8 ± 5.4 MPa to 2.07 ± 0.3 MPa in GL5). These physical alterations appear to facilitate rapid initial cell attachment while potentially compromising long-term stable adhesion through traditional integrin-mediated mechanisms. This study provides novel insights into the complex dynamics of MSC adhesion to glycated collagen, revealing previously unknown temporal patterns and challenging existing models of cell–matrix interactions. The findings suggest a need for revised approaches in tissue engineering and regenerative medicine, particularly in conditions where glycated collagen is prevalent. Full article