Search Results (9,150)

An anti-inflammatory dietary pattern represents a key component of non-pharmacological management in obesity and metabolic syndrome (MetS), as it targets chronic low-grade inflammation, adipose tissue dysfunction, insulin resistance, and disturbances of the gut–metabolic axis. In the present work, we outline a framework for an “omics-based” approach that integrates data on gut microbiota composition and function (metagenomics), adipokine profiles, nutrigenomics, epigenetics, and related transcriptomic and metabolomic layers in order to enable more precise characterization of the metabolic phenotype and to support precision nutrition strategies. The proposed dietary model emphasizes the quality rather than merely the quantity of macronutrients, with particular focus on lipid profile optimization. Specifically, total fat intake is recommended to remain below 30% of total energy through the reduction in saturated fatty acids (SFA), trans fats, and excessive omega-6 fatty acids, alongside increased consumption of omega-3 PUFA (EPA/DHA) and plant-based sources of α-linolenic acid (ALA). Concurrently, greater intake of lean protein sources and low-glycemic-index carbohydrates rich in dietary fibre—particularly fermentable fractions—is recommended. The model also highlights the importance of polyphenols with antioxidant and immunomodulatory properties. To enhance feasibility and long-term adherence, recommendations are structured as flexible food substitutions rather than rigid prescriptions. Further well-designed interventional studies are required to confirm the impact of a multi-omics-based anti-inflammatory diet on both molecular and clinical endpoints. Full article

Background: Microbial fermentation of non-digestible carbohydrates and proteins produce short-chain fatty acids (SCFAs), which are critical communication signals in the gut–adipose tissue axis. Individual SCFA can differentially modulate the adipocyte secretory profile and adipose tissue metabolic function; however, their dose-dependent effects on adipocyte function in combined inflammatory and hypoxic environmental conditions that reflect the obesity-associated adipose tissue phenotype remain unknown. Methods: Mature 3T3-L1 adipocytes were cultured for 24 h with lipopolysaccharide (LPS; 10 ng/mL) plus 100 µM of cobalt chloride (CoCl₂) to chemically induce hypoxia ± individual SCFAs, namely acetate (Ace), propionate (Pro), and butyrate (But), in a dose-dependent manner (0.25 mM, 0.5 mM, and 1 mM). Results: Ace, Pro and But reduced secretion of IL-6, MCP-1/CCL7 and Rantes/CCL5 in a dose-dependent manner, whereas Pro and But reduced MCP3/CCL7 secretion and only But reduced resistin and increased adiponectin secretion compared to control (p < 0.05). Intracellular protein expression of the ratio of phosphorylated–to–total NFκB p65 was reduced by 1 mM But, whereas the ratio of phosphorylated–to–total STAT3 expression was reduced by 1 mM Ace, Pro and But and 0.5 mM Pro and But compared to control (p < 0.05). There was no difference in insulin-stimulated or non-insulin-stimulated glucose uptake between control and any individual SCFAs (p > 0.05). Conclusions: Adipocyte adipokine secretory function in combined inflammation and hypoxic environmental conditions is dose-dependently attenuated by individual SCFA, which exhibit both individual and overlapping effects. Full article

Background/Objectives: While sarcopenia has been implicated, we hypothesize that a distinct body composition phenotype, characterized by elevated visceral adiposity and reduced abdominal muscle mass, plays a more critical role in T2DM-related fracture pathogenesis. Methods: In a cross-sectional study of 99 female patients aged ≥65 years who underwent surgery for hip fracture, we compared body composition parameters derived from DXA scans between those with (n = 40) and without (n = 59) T2DM. Key measures included appendicular lean mass index (ALMI), visceral adipose tissue (VAT) mass, android-to-gynoid (A/G) fat ratio, and a derived measure of relative core lean mass (RCLM). Results: There were no significant differences in ALMI between T2DM and non-DM groups. In contrast, T2DM showed significantly higher central adiposity—A/G ratio (1.13 ± 0.15 vs. 1.05 ± 0.17; p = 0.0298) and TL fat ratio (1.31 ± 0.22 vs. 1.19 ± 0.23; p = 0.0071)—with VAT estimate numerically higher. Conclusions: In older hip-fracture patients, T2DM was characterized not by appendicular sarcopenia but by central adiposity without significant differences in LMI or RCLM—a phenotype that may contribute to fracture risk through bone-quality and fall-related pathways independent of ALMI. Full article

Background/Objectives: The fundamental classification based on white, brown, pink, and beige adipose tissue morphology together with fat vacuole content released into the tumor microenvironment incompletely defines breast cancer-associated adipose tissue (BCAAT) heterogeneity and does not sufficiently explain its controversial impact on invasion, recurrence, or survival in breast cancer (BC). We aim to expand BCAAT characterization by systematically evaluating stromal cellular elements within peritumoral adipose tissue, including CD34-positive fibroblasts, smooth muscle actin (SMA)-positive myofibroblasts, inflammatory cells, and microvascular structures to define distinct BCAAT subgroups. Methods: CD34 and smooth muscle actin (SMA) double immunohistochemistry was performed on 109 BC tissue specimens from patients aged 35 to 79 years old, followed by microscopic evaluation of cellular and vascular components inside peritumor adipose tissue. Microscopic findings were then correlated to age, body mass index (BMI), lymphovascular (LVI) and perineural invasion (PnI), recurrence (R), and tertiary lymphoid structures (TLSs). Results: Four BCAAT subtypes have been identified as fibroblast-rich (F^Rich_BCAAT), myofibroblast-rich (MyoF^Rich_BCAAT), vascular-rich (V^Rich_BCAAT), and mixed-vascular and inflammatory-rich (VI^Rich_BCAAT). The F^Rich_BCAAT subtype predominates for the age subgroup 35 to 49 years old and is a significantly worse prognostic factor for survival (p = 0.022). For the age subgroup of 50 to 69 years old, the VI^Rich_BCAAT subtype significantly influences PnI (p = 0.05) but not survival (Log-rank test, z = 0.57, p = 0.57). V^Rich_BCAAT was significantly impactful for BC patient survival aged 70 to 75 years old (p = 0.043). BMI did not correlate with any of the BCAAT subtypes but was strongly correlated with prognostic markers for each BCAAT subtype. Conclusions: Based on immunohistochemically detected cellular and vascular components, four microscopic BCAAT subtypes were identified. Three of four BCCAT subtypes specifically affect BC patient prognosis and survival depending on age. Full article

The loss of estrogen following menopause is associated with a marked increase in cardiometabolic risk, accompanied by adverse changes in lipid metabolism, insulin sensitivity, vascular function, and systemic inflammatory tone. Emerging evidence suggests that estrogen signaling interacts with chromatin regulatory mechanisms, including DNA methylation, histone modifications, and chromatin remodeling, across multiple metabolic tissues. In this review, we examine current evidence linking estrogen receptor signaling to epigenetic modulation in cardiovascular, hepatic, adipose, vascular, and immune systems. We propose that epigenetic remodeling represents a plausible and testable mechanistic framework connecting estrogen depletion to cardiometabolic disease progression, while acknowledging that much of the mechanistic evidence derives from preclinical and in vitro systems and that direct longitudinal validation in human cardiovascular tissues remains limited. We further explore how this framework may contribute to understanding the “estrogen paradox” and the heterogeneous outcomes of hormone replacement therapy (HRT), particularly within the context of the timing hypothesis. Finally, we evaluate pharmacologic and lifestyle interventions, including structured exercise, dietary modulation, and cardiometabolic therapeutics, through the lens of potential epigenetic influence. Clarifying tissue-specific and immune-integrated chromatin responses to estrogen loss will be essential for advancing precision strategies aimed at improving cardiometabolic health in postmenopausal women. Full article

Purpose: Castration-resistant prostate cancer (CRPC) responds poorly to conventional chemotherapy. We evaluated a cell-based enzyme–prodrug therapy using adipose-derived stem cells (ADSCs) engineered to express cytosine deaminase (CD) or carboxylesterase 2 (CE2), paired with their respective prodrugs 5-fluorocytosine (5-FC) or irinotecan (CPT-11), to compare their antitumor efficacy. Materials and Methods: Human telomerase reverse transcriptase (hTERT)-immortalized ADSCs were transduced with CD or CE2, and transgene expression and stem cell phenotype were confirmed. CD expression was verified at the transcript level and by functional 5-FC-to-5-fluorouracil (5-FU) conversion, whereas CE2 expression was verified by transcript analysis and immunoblotting. Tumor tropism toward PC3 prostate cancer cells was tested using migration assays and analysis of chemoattractant ligand/receptor expression. Prodrug-induced self-killing and bystander tumor cell killing were assessed through viability assays and co-culture with PC3 cells. For the CE2/CPT-11 system, SN-38 was not directly quantified; functional activity was inferred from prodrug-dependent cytotoxicity and in vivo efficacy. In vivo efficacy was evaluated in nude mice with PC3 tumors treated systemically with engineered ADSCs plus prodrug. Results: CD- and CE2-expressing ADSCs were successfully established and retained mesenchymal stem cell (MSC) characteristics. Both cell types exhibited significant migration toward PC3 cells. The CE2/CPT-11 system produced stronger prodrug-mediated cytotoxicity than CD/5-FC, with CE2-modified ADSCs showing higher sensitivity to CPT-11 and inducing greater apoptosis in co-cultured PC3 cells. In vivo, both treatments suppressed tumor growth, but CE2/CPT-11 achieved greater inhibition (tumor volume ~26% of control vs. ~32% for CD/5-FC at day 14). No overt clinical toxicity was observed based on body weight and daily clinical monitoring; however, hematology/serum chemistry were not assessed. Conclusions: Engineered ADSCs home to CRPC tumors and enable local prodrug activation, producing significant antitumor effects. Within the constraints of our in vitro assays and subcutaneous xenograft model, CE2/CPT-11 demonstrated stronger efficacy outcomes than CD/5-FC. Mechanistic attribution to intratumoral SN-38 exposure should be confirmed by direct metabolite measurements in future studies. Full article

Sodium–glucose cotransporter 2 inhibitors (SGLT2is) have revolutionized the treatment of heart failure and are now established as disease-modifying therapies across the spectrum of left ventricular ejection fraction. More recently, these agents have been evaluated in the early post-acute myocardial infarction (AMI) setting, raising interest in their potential role beyond heart failure prevention. Evidence from post-AMI randomized trials and contemporary meta-analyses consistently shows neutral effects on ischemic coronary outcomes, despite favorable effects on heart failure-related endpoints, ventricular remodeling, and cardiometabolic parameters. At the same time, data from experimental and translational research provide a biological framework in which SGLT2i exert anti-atherogenic effects through multiple complementary mechanisms, including improvement of cardiometabolic risk factors, attenuation of vascular and systemic inflammation, modulation of endothelial function, regulation of vascular smooth muscle cell behavior, macrophage inflammatory polarization, inhibition of inflammasome signaling, and modulation of the perivascular adipose tissue–vascular interface. Taken together, the available evidence highlights a dissociation between clinical trial outcomes in the early post-AMI phase and the underlying vascular biology associated with SGLT2 inhibition. While the dominant early clinical effects of SGLT2i appear to relate to hemodynamic and heart failure-preventive mechanisms, their potential impact on atherosclerotic disease may be more gradual and context-dependent. This review summarizes current clinical and mechanistic evidence supporting this interpretation and discusses the implications for understanding the role of SGLT2i in patients after AMI. Full article

Olive pomace, a byproduct of olive oil production, is a rich source of bioactive phenolic compounds with potential health benefits. This study aimed to characterize the chemical composition and evaluate the metabolic effects of a subcritical water extract from California olive pomace (SWE COP) obtained from Arbequina olives. The extract was mainly composed of carbohydrates (72.81%) and contained 66.62 ± 1.22 mg gallic acid equivalents/g of phenolics, with 3,4-DHPEA-EDA, hydroxytyrosol, and verbascoside identified as the predominant compounds. Male C57BL/6N mice were fed a standard diet (SD; n = 7), a high-fat and high-sugar diet (HFSD; n = 7), which was used to induce features of diet-associated metabolic syndrome, or an HFSD supplemented with 3% (w/w) SWE COP (n = 7) for 16 weeks. Supplementation with SWE COP significantly reduced plasma triglycerides and increased HDL cholesterol levels compared with the HFSD group. Moreover, SWE COP improved glucose tolerance, enhanced insulin sensitivity, and reduced mesenteric and epididymal adiposity. Histological analysis showed that SWE COP alleviated hepatic steatosis and lowered the NAFLD activity score. These findings demonstrate that phenolic-rich SWE COP exerts beneficial effects on glucose and lipid metabolism and reduces liver fat accumulation in diet-induced obese mice. Overall, SWE COP represents a promising functional ingredient derived from olive industry byproducts for mitigating metabolic dysfunctions associated with obesity. Full article

Soft tissue sarcomas are rare malignant mesenchymal tumors for which accurate diagnosis, prognostic stratification, and therapeutic decision-making remain challenging. Although histopathology and immunohistochemistry are essential diagnostic tools, they frequently fail to capture the molecular complexity underlying tumor aggressiveness and treatment resistance. In this study, we evaluated the utility of RNA-based next-generation sequencing for the molecular characterization of STS and for elucidating transcriptomic mechanisms associated with aggressive tumor behavior. An observational cohort of 24 patients with histologically confirmed soft tissue sarcomas was analyzed, using adipose and skeletal muscle tissue as controls. RNA was extracted from tumor samples, libraries were prepared with a targeted pan-cancer panel, and sequencing was performed on the Illumina platform, followed by bioinformatic analysis using DRAGEN pipelines and DESeq2. RNA-NGS identified a predominance of single-nucleotide polymorphisms and significant differential gene expression, with overexpression of proliferation-related genes (TOP2A, MKI67, BUB1B), extracellular matrix and microenvironment-associated genes (COL11A1, SPP1), and developmental regulators (HOXD13, MELK). Subgroup analysis revealed a distinct transcriptomic profile in leiomyosarcoma, while gene fusion analysis detected clinically relevant alterations. These findings demonstrate that RNA-NGS provides biologically and clinically meaningful insights into the molecular landscape of soft tissue sarcomas and supports its integration into precision medicine-oriented diagnostic workflows. Full article

Introduction/Objectives: Body composition changes and diet quality may contribute to metabolic complications and graft outcomes after kidney transplantation. We evaluated the relationships between diet quality and CT-derived body composition components (skeletal muscle mass, muscle quality/myosteatosis, and visceral adiposity) and explored their associations with metabolic markers and graft function. Materials and Methods: In this single-center retrospective cross-sectional study, we included 161 adult first kidney transplant recipients (KTRs) with a functioning graft and ≥12 months of follow-up. Body composition was quantified on routine abdominal CT at the L3 level using skeletal muscle index (SMI), mean muscle attenuation (Hounsfield units) for myosteatosis, and visceral adipose tissue area (VAT). Diet quality was scored using the Revised Diet Quality Index (DQI-R). Graft function was followed with creatinine-based estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI equation. Results: Mean age was 45.7 ± 13.2 years and 58% were men. The prevalence of low muscle mass was 26.0%, myosteatosis 73.5%, and visceral obesity (VAT ≥ 100 cm²) 45.6%. No participant had “good” diet quality; 48.4% had poor diet quality. DQI-R showed a weak positive correlation with SMI (r = 0.157; p = 0.047) but was not significantly related to VAT, subcutaneous adipose tissue (SAT), Kidney transplant recipient (VSR) or myosteatosis. In multivariable models, age and VAT were associated with HbA1c, whereas body composition and diet quality variables were not independent predictors of eGFR. Myosteatosis was independently associated with older age. Conclusions: Visceral adiposity and impaired muscle quality frequently clustered and were linked to metabolic status. These findings support post-transplant follow-up strategies that go beyond BMI and integrate body composition and nutritional assessment within a multidisciplinary care model. Full article

Obesity is characterized by abnormal adipose tissue expansion and energy metabolism imbalance. Browning of white adipose tissue (WAT), wherein white adipocytes acquire thermogenic properties similar to brown adipose tissue, represents a key mechanism for increasing energy expenditure. Although ginseng (Panax ginseng C.A. Meyer) is widely recognized as a health-promoting botanical, its role in WAT browning has not been fully elucidated. This review summarizes evidence that ginseng and its bioactive components regulate major thermogenic pathways, including β-adrenergic/cyclic adenosine monophosphate-protein kinase (cAMP-PKA) signaling, AMP-activated protein kinase (AMPK), and the peroxisome proliferator-activated receptor γ (PPARγ)/coactivator 1α (PGC-1α) axis, thereby upregulating key markers such as uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16) and type II iodothyronine deiodinase (DIO2). These effects promote mitochondrial function and fatty acid oxidation, reduce lipogenesis, alleviate inflammation, and improve insulin sensitivity, collectively fostering a microenvironment conducive to browning. Furthermore, fermentation has been found to enhance the bioactivity and thermogenic efficacy of ginseng. Recent evidence indicates that gut microbiota and their metabolites—such as short-chain fatty acids, unsaturated fatty acids, and bile acids—play a notable role in ginseng-induced thermogenesis via receptors including G-protein-coupled receptor 41/43 (GPR41/43), takeda G-protein-coupled receptor 5 (TGR5), and farnesoid X receptor (FXR). These multi-organ interaction networks involving the gut–fat, gut–liver, and gut–brain axes reflect the role of ginseng in integrating systemic metabolism. In summary, this review discusses the multi-level regulatory network through which ginseng promotes WAT browning, providing a mechanistic basis for its potential application in body weight and metabolic health management. Full article

Adipose tissue serves as a critical metabolic and endocrine organ, essential for maintaining systemic energy homeostasis and inter-organ communication. During the aging process, it undergoes significant structural remodeling and functional decline, characterized by dysregulated lipid metabolism, chronic low-grade inflammation, reduced insulin sensitivity, and adipokine imbalance. These alterations not only compromise the physiological integrity of adipose tissue but also contribute to the progression of various age-associated metabolic disorders, including type 2 diabetes, atherosclerosis, and nonalcoholic fatty liver disease. In recent years, natural products have emerged as a focal point in anti-aging research, owing to their broad accessibility, high biological safety, and capacity for multi-target regulation. Polyphenolic and polysaccharide, in particular, have demonstrated robust antioxidant, anti-inflammatory, autophagy-modulating, and mitochondrial-protective effects in cellular and animal models, indicating their promise in attenuating adipose tissue aging. Although the anti-aging effects of these natural compounds are well documented in the neural, hepatic, and cardiovascular systems, their specific mechanisms in adipose depots—especially differential regulatory patterns between white and brown adipose tissues, which may inform depot-specific therapies—and the development of targeted delivery approaches remain inadequately explored. This review, grounded in the three primary hallmarks of adipose tissue aging (oxidative stress, chronic inflammation, and dysregulated lipid metabolism), systematically elucidates the molecular mechanisms and recent advancements in the application of polyphenols and polysaccharides as natural modulators. This review establishes a cohesive theoretical foundation and delivers innovative perspectives to guide the advancement of natural product-based nutritional and therapeutic strategies for combating adipose tissue aging. Full article

Background/Objectives: This exploratory study (n = 6 per group) investigated the associations between supplementation with α-lipoic acid (AL), betaine (BT), and L-carnitine (LC) and gut microbiota composition in a high-fat diet (HFD)-induced obesity mouse model. Methods: Four-week-old male C57BL/6J mice were fed a control diet (10% fat), HFD (60% fat), or HFD supplemented with AL, BT, or LC (300 mg/kg BW/day) for nine weeks. Results: All three compounds were associated with shifts in microbial composition compared to the HFD-only group. While AL and BT supplementation moderately modulated specific Firmicutes and Bacteroidetes taxa, LC supplementation was linked to a more pronounced reduction in the Firmicutes/Bacteroidetes ratio and a decreased abundance of genera such as Christensenellaceae, Lachnospiraceae, and Coprococcus 3. These microbial changes were correlated with obesity-related metabolic and adiposity markers, including leptin and lipid parameters. Furthermore, functional profiling via PICRUSt suggested potential alterations in amino acid metabolism; however, these findings represent inferred metabolic potential rather than direct metagenomic measurements. Conclusions: Collectively, these results indicate differential associations between dietary supplementation and gut microbiota composition in HFD-fed mice. Although this study was conducted within an exploratory framework and utilized a modest sample size, the observed microbial shifts consistently paralleled metabolic alterations, supporting biologically plausible associations that warrant further mechanistic investigation. Full article

Background: Periprostatic adipose tissue (PPAT) fibrosis is a histological feature potentially linked to prostate cancer (PCa) aggressiveness, though its role is not fully understood. This study investigates the correlation between PPAT fibrosis and PCa aggressiveness and develops a radiomics model based on PPAT MRI features for non-invasive prediction. Methods: This retrospective study included 51 patients who underwent radical prostatectomy. PPAT samples were collected, stained with Sirius Red and quantitatively evaluated for fibrosis using 12 indices via 3D reconstruction with Imaris software. Patients were stratified by cancer aggressiveness based on Grade Groups. Radiomic features were extracted from T1-weighted MRIs of the PPAT. An XGBoost model was developed to predict aggressiveness using these features. Results: Significant correlations were found between multiple PPAT fibrosis indices and PCa aggressiveness (p < 0.05), with more aggressive tumors showing increased fiber complexity. PPAT fibrosis was also significantly associated with primary tumor location in the peripheral zone (p < 0.05). Conversely, PPAT volume showed no significant correlation with aggressiveness (p = 0.616). The radiomics model based on PPAT features achieved an AUC of 0.86 in predicting cancer aggressiveness. Conclusions: PPAT fibrosis is a promising marker of PCa aggressiveness, superior to PPAT volume. The significant link with tumor location provides new insights into the tumor microenvironment (TME). MRI-based radiomics of PPAT offers a potential non-invasive method for assessing fibrosis and aggressiveness, aiding in early diagnosis and personalized treatment. Full article

Background/Objectives: Bile duct ligation (BDL), characterized by marked inflammation and fibrosis, effectively mimics many clinical conditions and is a valuable tool for investigating biliary regeneration. Our objective was to clarify the therapeutic benefits of adipose-derived stem cell (ADSC) treatment and signaling pathways mediating regenerative processes in a rat model of BDL. Methods: The BDL model was performed on Sprague–Dawley rats, and ADSC was administered intrasplenically at a dose of 10⁶ cells per animal. Liver function tests, gene and protein expression analyses, histological evaluation, and immunohistochemistry staining were performed to assess liver function, signaling pathways, inflammation, and fibrosis. Results: ADSC treatment returned liver function to sham levels. ADSC upregulated the Hes1 gene and protein expression in the early and late term. Inflammation, fibrosis, and total damage scores were decreased following ADSC treatment compared with the control. Immunohistochemistry staining revealed higher CD90, CD44, and CD29 stem cell marker expression in the ADSC treatment group. Conclusions: ADSC administration reduced fibrosis and biliary damage and restored liver function, potentially in a manner mediated by upregulated Hes1 expression, supporting its promise in biliary regeneration. Full article