Search Results (3,108)

Metabolic syndrome (MetS) is a major driver of cardiovascular disease, renal injury, and hepatic steatosis, largely through chronic low-grade inflammation and oxidative stress. This study evaluated the cardioprotective, nephroprotective, and hepatoprotective potential of a polyphenol-rich fraction (PP) isolated from Ilex aquifolium leaves in obese Zucker (fa/fa) rats—a well-established model of MetS. Male rats (8 weeks old) were randomly assigned to receive either a standard diet (CTRL, n = 8) or the same diet supplemented with 10 mg/kg body weight/day of the polyphenol fraction (PP, n = 8) for 8 weeks. The fraction was dominated by chlorogenic acid (59.33 mg/g), neochlorogenic acid (35.39 mg/g), and rutin (9.23 mg/g). At the end of the experiment, biochemical markers of oxidative stress, inflammation, and metabolic status were assessed, together with detailed histopathological examination of the heart, kidneys, and liver. Supplementation with Ilex aquifolium polyphenols significantly increased (p < 0.01) total antioxidant status, reduced circulating IL-6 and increased MCP-1 levels. These changes were accompanied by clear cardioprotective effects. However, the intervention also produced organ-specific adverse effects. In the kidneys, polyphenol-treated rats exhibited histopathological features consistent with early-stage nephropathy. In the liver, supplementation exacerbated hepatic steatosis compared to controls. In conclusion, the polyphenol-rich fraction from Ilex aquifolium exerts potent antioxidant and anti-inflammatory effects that translate into substantial cardioprotection in obese Zucker rats. Nevertheless, its capacity to worsen renal injury and hepatic steatosis highlights the need for caution and further dose- and duration-dependent studies before considering therapeutic application in metabolic syndrome. Full article

Amomum tsaoko Crevost & Lem. (AT) is a representative edible, medicinal spice widely used in Southeast Asia for food seasoning and flavor enhancement. Growing evidence suggests that it is a rich source of bioactive phytochemicals with diverse health-promoting properties, necessitating a systematic synthesis of its functional attributes and underlying mechanisms to better guide future applications. AT has been reported to contain flavonoids, diarylheptanoids, phenolic acids, terpenoids, steroids, and volatile oils. These constituents are associated with a broad spectrum of biological activities, including antimicrobial, antidiabetic, antioxidant, anti-inflammatory, anticancer, neuroprotective, anti-obesity, gastrointestinal protective, and immunomodulatory effects. Due to its functional properties and economic value, AT shows considerable potential for application in functional foods, pharmaceuticals, cosmetics, and agriculture. However, despite its extensive utilization, integrated reviews that systematically link bioactivities, toxicological evidence, and industrial applications remain scarce. This review comprehensively summarizes recent advances in the bioactive compounds, health functions, toxicological evaluation, and industrial applications of AT. Current research progress, key limitations, and future perspectives are critically discussed. Additionally, by providing a comprehensive overview of its multifaceted benefits and applications, this review fills an important gap and offers insights to support further research and multi-sectoral exploitation of AT. Full article

Obesity is a complex, chronic, relapsing disease that affects nearly all physiological functions and homeostatic mechanisms, extending far beyond mere excess adiposity. Traditional clinical practice often relies on uniform interventions that fail to account for diverse patient phenotypes. This review synthesizes current evidence on personalized obesity management, dietary interventions, and advanced pharmacotherapies aligned with the new 2025 Lancet Commission framework. A comprehensive narrative review was conducted across major biomedical databases to evaluate the efficacy, safety, and mechanisms of metabolic interventions, focusing on phenotype-specific dietary matching, bioactive compounds, and modern multi-receptor glucagon-like peptide-1 (GLP-1)-based therapies across preclinical and clinical intervention tiers in adult and pediatric populations. While specific nutraceutical extracts display promising secondary metabolic benefits, their overall weight-loss efficacy remains modest due to variable clinical data and limited sample sizes. Conversely, high-potency anti-obesity medications demonstrate unprecedented weight-reduction efficacy, with semaglutide 2.4 mg and tirzepatide yielding mean body weight losses of ~14.9% and ~20.9%, respectively. Furthermore, landmark outcome data from the SELECT trial confirms that semaglutide 2.4 mg achieves a significant 20% relative risk reduction in major adverse cardiovascular events (MACE), independent of baseline glycemic status or heart failure. However, clinical extension data reveal rapid weight rebound upon drug cessation, highlighting that obesity requires continuous, long-term therapeutic strategies. Effective obesity care demands an operational shift from traditional, one-size-fits-all treatments to personalized, multi-tiered strategies. Combining phenotype-specific lifestyle modifications with potent, long-term multi-hormonal pharmacotherapies or metabolic surgery optimizes long-term therapeutic durability, systemic metabolic health, and sustained cardioprotection. Full article

Background: MASLD is a disorder linked to lipid metabolism and obesity, increasingly prevalent among sedentary people and leading to hepatic fibrosis. Cyclodipeptides (CDPs) have promising anti-obesogenic and liver-protective potential. Methods: CDP treatment was evaluated in a chronic MASLD model using female Wistar rats fed an obesogenic diet, with assessments of insulin resistance, glucose tolerance, liver damage, oxidative stress, and the expression of genes related to metabolic function. Results: MASLD CDP-treated rats showed low visceral adipose tissue (VAT) content, improved insulin responsiveness and glucose tolerance, reduced steatosis, and reversed oxidant stress and the NRF2, GPX1, and GCLC expression. Furthermore, MASLD-related dysregulation of genes involved in lipid metabolism was restored, including vLDL transport (MTTP, APOB, and RASAL2), β-oxidation (PPAR-α, ACOX1, and FOXO1), lipogenesis (ACC1 and SREBP 1C), and fatty acid transport (PSD3 and CD36). In accordance, genes of key signaling pathways were also restored, including mTOR, TSC1, and TSC2, along with fibrosis and inflammation TGF-β, Fas, NF-κB, and IL-6. In VAT of MASLD animals, crown-like structures and adiposity density were diminished by CDP treatment, with increased expression of genes associated with beige-like adipose tissue remodeling, including PGC-1α, UCP1, NRF1, ATP6v1, CEBP-α, COX4i1, PPARγ, and CS. Consistently, the UCP1 and PGC-1α protein expression was increased in the VAT of MASLD animals treated with CDPs. Conclusions: The anti-MASLD effects of CDPs were associated with reversal of key pathogenic markers in the liver and VAT, suggesting remodeling of white adipose tissue (WAT) toward a beige-like adipose tissue phenotype. The findings suggest that CDPs may modulate adipose tissue structure and adipogenesis, underscoring their therapeutic relevance for MASLD. Full article

Background: Pharmacological blockade of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has emerged as an attractive pharmacological strategy for a broad range of inflammatory and metabolic disorders. However, translating preclinical efficacy into clinical success remains a major bottleneck. We previously reported the discovery of a novel, potent NLRP3 inhibitor, KBD3536, but its in vivo efficacy across different pathological conditions remains uncharacterized. Here, we systematically evaluated the in vivo efficacy of KBD3536 across diverse preclinical models of NLRP3-related pathologies. Methods: KBD3536 was evaluated in established rodent models of monosodium urate (MSU)-induced acute inflammation (mouse air pouch and rat gouty arthritis models), radiation-induced dermatitis (RID), and high-fat diet (HFD)-induced obesity. Results: In the MSU models, KBD3536 markedly suppressed local interleukin-1β and interleukin-6 secretion in air pouch exudates and dose-dependently alleviated acute arthritis symptoms, including joint swelling and joint pain. In the RID model, KBD3536 significantly attenuated radiation-induced skin injury and ameliorated radiation-induced systemic weight loss. Under HFD challenge, early intervention with KBD3536 mitigated HFD-induced adiposity, early hepatic steatosis and its associated inflammatory responses, and preserved physical performance. Mechanistically, KBD3536 partially restored AMP-activated protein kinase α1 (AMPKα1) mRNA expression in adipose tissue and restored hepatic Cyp3a11 transcriptional activity. Conclusions: NLRP3 inhibitor KBD3536 exhibited broad-spectrum anti-inflammatory efficacy across multiple preclinical models, supporting its potential as a promising candidate for diverse NLRP3-related disorders. Full article

Background and Objective: Helicobacter pylori infection remains a major cause of chronic gastritis, dyspepsia, and peptic ulcer disease worldwide. Increasing antibiotic resistance, particularly to clarithromycin, has reduced the effectiveness of standard eradication therapies. The aim of this study was to compare the effectiveness of two triple therapy regimens for Helicobacter pylori eradication in patients presenting with dyspepsia in primary care and to evaluate the influence of demographic, clinical, and lifestyle factors on treatment outcomes. Methods: This retrospective study included 1800 adult patients with dyspeptic symptoms and confirmed Helicobacter pylori infection who received triple therapy between January 2023 and early 2026 in a primary care setting. Patients were treated with either clarithromycin 500 mg, amoxicillin 1000 mg, and pantoprazole 20 mg, or levofloxacin 500 mg, amoxicillin 1000 mg, and pantoprazole 20 mg. Clinical reassessment and therapy review were performed after 21 days. Eradication status was evaluated using stool antigen testing after completion of therapy. Data extracted from medical records included age, sex, body mass index, smoking status, alcohol consumption, obesity, diabetes mellitus, history of gastroduodenal disease, and chronic use of non-steroidal anti-inflammatory drugs. Statistical analysis included descriptive statistics, chi-square testing, and multivariable logistic regression to identify factors associated with eradication success. Statistical significance was considered at p < 0.05. Results: Among 1800 patients, 52 percent were male and the mean age was 47 years. The levofloxacin-based regimen achieved a significantly higher eradication rate compared with the clarithromycin-based regimen, 82.9 percent versus 71.8 percent, p < 0.001. Treatment failure was more frequent among active smokers, obese patients, alcohol consumers, and individuals with diabetes mellitus. In multivariable analysis, treatment with a levofloxacin-based regimen remained an independent predictor of successful eradication with an odds ratio of 1.88 and p < 0.001. Smoking, obesity, and diabetes were independently associated with lower eradication success. Adverse effects were reported in 13.9 percent of patients receiving clarithromycin and 9.1 percent of those receiving levofloxacin, with a statistically significant difference between the groups, p = 0.002. Conclusions: Levofloxacin-based triple therapy demonstrated superior effectiveness compared with the clarithromycin-based regimen for Helicobacter pylori eradication in patients with dyspepsia in primary care. Lifestyle factors and metabolic comorbidities appear to influence treatment outcomes and should be considered when selecting eradication strategies in routine clinical practice. Full article

Background/Objectives: Cellular senescence refers to a state where the phenotype of cells changes, and the cell cycle comes to a halt. Cellular aging occurs due to various causes and is implicated in the development of various age-related diseases. While the component filbertone in hazelnuts is known for its anti-obesity, anti-neurodegenerative, and anti-inflammatory effects, its potential anti-aging effects have not been elucidated. This study investigated whether filbertone modulates cellular senescence via the tumor suppressor protein p53 and its downstream target p21 in AML12 hepatocytes. Methods: AML12 hepatocytes were treated with doxorubicin or hydrogen peroxide, with or without filbertone (25–100 μM), in both an acute stress-induction model and an established senescent-cell model. p53 and p21 expression, senescence-associated β-galactosidase (SA-β-gal) staining, and the expression of senescence-associated secretory phenotype (SASP)-related cytokines (Il-1β, Il-6, Tnf-α) were assessed. Results: The results demonstrated that filbertone dose-dependently reduced the increased p53 and p21, a downstream gene of p53, induced by doxorubicin and hydrogen peroxide. Furthermore, the number of hepatic senescent cells with senescence-associated β-galactosidase staining was significantly decreased in the presence of filbertone. Filbertone treatment also significantly suppressed the expression of senescence-associated secretory phenotype (SASP)-related pro-inflammatory cytokines, including Il-1β, Il-6, and Tnf-α, in both stress-induced and established senescent hepatocytes. Conclusions: These findings indicate that filbertone modulates senescence-associated p53–p21 signaling and the accompanying inflammatory secretory phenotype in an in vitro model of AML12 hepatocytes, suggesting that filbertone may be a geroprotective compound that attenuates cellular senescence. Full article

Background: Glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R) activation exert anti-diabetic and anti-obesity effects. Tirzepatide, a dual GIPR/GLP-1R agonist, has demonstrated cardiovascular benefits in clinical studies. However, the direct vascular actions of tirzepatide and their potential advantages over selective GLP-1 receptor agonists (GLP-1RAs) remain unclear. We investigated the vasoprotective effects of tirzepatide and compared them with those of GLP-1 receptor agonists in vivo and in vitro. Methods: Non-diabetic C57BL/6 and diabetic KK-Ay mice received tirzepatide, semaglutide, or vehicle. Arterial remodeling was induced by femoral artery wire injury. A subset of mice was co-treated with the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME). After 4 weeks, biochemical, morphometric, and immunofluorescence analyses were performed. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated with tirzepatide or liraglutide to assess nitric oxide (NO) production. Results: In non-diabetic mice, tirzepatide suppressed intimal hyperplasia, including at a low dose that did not affect metabolic parameters, whereas semaglutide had no significant effect on intimal hyperplasia at the same molar dose. The protective effects of tirzepatide were abolished by L-NAME. In diabetic mice, tirzepatide and semaglutide similarly improved metabolic parameters and attenuated intimal hyperplasia. In HUVECs, tirzepatide increased NO production in a dose-dependent manner, and this effect was preserved under hyperglycemic conditions. Tirzepatide and liraglutide induced comparable NO production at equivalent molar concentrations. Conclusions: Tirzepatide, but not semaglutide, exerted vasoprotective effects under non-diabetic conditions in a NO-dependent manner, whereas both agents exhibited comparable vasoprotective effects under diabetic conditions. Full article

Background: Obesity has evolved from a morphometric descriptor to a chronic, relapsing, multisystem disease in which low-grade adipose-tissue inflammation, insulin resistance, endothelial dysfunction, and a prothrombotic, pro-tumorigenic milieu coexist. Venous thromboembolism (VTE) and malignancy share this substrate through a well-established bidirectional link: within twelve months of an unprovoked deep vein thrombosis (DVT), 6–15% of patients are diagnosed with occult cancer, a substantial proportion of which are already locally advanced or metastatic at detection. In this context, obesity acts as a dual amplifier of both thrombotic and oncologic risk, making the post-DVT patient with an incidentally diagnosed cancer a paradigmatic candidate for integrated management. Objective: To propose an evidence-based, unifying cardiometabolic and antithrombotic clinical framework that reconciles (i) risk-stratified screening for occult malignancy after unprovoked DVT, (ii) contemporary pharmacotherapy of obesity, and (iii) cancer-associated thrombosis (CAT) management, in the light of evidence published through 2025. Methods: Narrative synthesis based on a structured literature search (PubMed/MEDLINE, Embase, Scopus; 2000–March 2025) of current guidelines (ISTH, ASH, ESC Cardio-Oncology, EASO) and pivotal randomized evidence on GLP-1 and dual GLP-1/GIP receptor agonists (semaglutide, tirzepatide), SGLT2 inhibitors (empagliflozin, dapagliflozin), and direct oral anticoagulants (DOACs), with critical interpretation of recent meta-analytic data on oncologic signals, cardiovascular outcomes, and bleeding safety. Results: Three evidence-based pillars emerge: (1) limited screening complemented by age- and sex-specific testing in patients ≥ 50 years with unprovoked DVT, enhanced by FDG-PET/CT for high-risk phenotypes in which obesity itself degrades the sensitivity of clinical examination and conventional imaging; (2) GLP-1/GIP receptor agonist-based anti-obesity pharmacotherapy, associated in observational cohorts with a 17% relative reduction in overall cancer incidence (HR 0.83; 95% CI 0.76–0.91) and neutral-to-reassuring oncologic signals, but requiring cautious, case-by-case use in patients with active cancer because of the risk of accelerating sarcopenia and cachexia; and (3) apixaban as the preferred DOAC for cancer-associated thrombosis, with a superior efficacy-to-bleeding ratio in network meta-analyses and a reduced-dose extended strategy now validated by the API-CAT trial. Conclusions: Patients with obesity presenting with unprovoked DVT and an incidentally detected cancer embody a cardiometabolic–antithrombotic continuum. A framework integrating structured occult-cancer screening, judicious obesity pharmacotherapy, and apixaban-preferred anticoagulation—coordinated by a multidisciplinary team and illustrated here by a case-based pathway—offers the most rational, evidence-aligned approach. Prospective, dedicated trials in this specific phenotype are urgently warranted. Full article

Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, have revolutionized the management of type 2 diabetes and obesity. Recent evidence suggests these agents may influence athletic performance through effects on body composition, energy metabolism, and cardiovascular function. This narrative review critically evaluates whether incretin therapies could constitute doping under World Anti-Doping Agency (WADA) criteria. We narratively reviewed the literature on incretin pharmacology, metabolic effects relevant to athletic performance, and anti-doping regulations, searching PubMed, Scopus, and Web of Science using terms including “GLP-1 receptor agonists”, “DPP-4 inhibitors”, “doping”, “athletic performance”, “WADA”, and “sports pharmacology”, without date restrictions. GLP-1 RAs (semaglutide, liraglutide, tirzepatide, exenatide) induce substantial weight loss (predominantly fat mass) but also reduce lean mass by 20–30% of total weight loss. Preclinical studies demonstrate enhanced exercise endurance, mitochondrial biogenesis, and glucose uptake via GLP-1R/AMPK signaling. However, clinical trials show no consistent improvement in physical performance in humans. Currently, incretin therapies are not listed on the WADA Prohibited List. While incretin therapies offer theoretical performance-enhancing potential through weight management and metabolic optimization, current evidence does not support classification as doping agents. Continued surveillance is warranted as misuse patterns emerge. Full article

Boiogito (BOT), a traditional Kampo herbal medicine, has been reported to exhibit anti-inflammatory and anti-obesity properties. However, its potential role in protecting adipocyte function under inflammatory conditions at different stages of adipocyte development remains unclear. This study investigated the effects of BOT on adipogenesis and tumor necrosis factor-α (TNF-α)-induced inflammatory responses in differentiating and mature 3T3-L1 adipocytes. In this study, 3T3-L1 preadipocytes were induced to differentiate and exposed to TNF-α in the presence or absence of BOT during differentiation or after full adipocyte maturation. Lipid accumulation was assessed by Oil Red O staining, while adipokine secretion and inflammatory cytokine production were evaluated by ELISA. The expression of adipogenic markers and inflammatory signaling molecules was analyzed using quantitative PCR and Western blotting. TNF-α significantly inhibited the expression of adipogenesis-related factors at the transcriptional level in adipocytes, reduced lipid accumulation and adiponectin expression, and enhanced inflammatory cytokine production. BOT treatment dose-dependently attenuated these effects, restoring adipogenic capacity and suppressing inflammatory responses in both differentiating and mature adipocytes. Mechanistically, BOT reduced TNF-α-induced activation of the NF-κB pathway, as evidenced by decreased phosphorylation of NF-κB p65 and IκB. These findings demonstrate that BOT preserves adipocyte function and mitigates inflammation-associated adipocyte dysfunction throughout adipocyte development. The protective effects of BOT may contribute to the regulation of obesity-associated metabolic inflammation, partly through modulation of NF-κB signaling. Full article

Background/Objectives: Obesity is a chronic and multifactorial disease, and the global prevalence of obesity-induced metabolic and systemic complications is expected to rise. Current peptide-based drugs that mainly target glucagon-like peptide-1 receptor activation have shown unprecedented efficacy in body weight reduction. Nevertheless, they show undesirable adverse effects including gastrointestinal effects, lean mass reduction, and rebound weight gain after ending pharmacotherapy. These underscore the medical need for additional anti-obesity drugs with novel pathways. Methods: Literature updating current anti-obesity pharmacotherapy and reporting potential drug targets and candidates in the last five years was searched across PubMed. The resulting literature was classified into working mechanisms and target receptors. Results: Recent research on incretin-based peptide drugs has focused on developing more convenient regimens by introducing longer-acting once-monthly injection or oral formulation. Novel anti-obesity targets other than incretin receptors have also been suggested. This narrative review summarizes recent research updates on peptide-based drugs and upcoming anti-obesity drug candidates tested in clinical and in vivo studies. Conclusions: Beyond the current peptide-based pharmacotherapy, novel anti-obesity drug candidates are waiting for further validation in clinical trials. When used alone or combined with the available drugs, these candidates may produce more effective and safer pharmacotherapy for obesity treatment. Full article

Molecular microbiology has revolutionized our understanding of the complex host-associated microbiomes required for normative development and physiology. Horses and other members of the family Equidae are particularly reliant on the early maturation and lifelong maintenance of an unusually rich hindgut microbiome for optimal digestion and overall health and performance. Research on the equine gut microbiome has accelerated in the past several years, necessitating a renewed appraisal of the field. The present work is a comprehensive and critical review of the literature regarding the bacterial gastrointestinal microbiome of horses. First, the developmental trajectory of the foal gut microbiome is discussed, followed by descriptions of the taxonomic membership of the core equine gut microbiome, its primary functions and effects on host physiology, and intrinsic and extrinsic factors that shape the equine microbiome during health, with a focus on diet and supplements. Next, evidence supporting adverse effects on the equine gut microbiome of gastrointestinal conditions including colic and colitis, extraintestinal conditions including obesity and laminitis, and pharmacological interventions including antibiotics and non-steroidal anti-inflammatory drugs is summarized. Lastly, clinical and experimental research investigating the effects of treatments targeting the gut microbiome of horses, including probiotics, prebiotics, and fecal microbiome transfer, is critically examined. Conclusions summarize the connection between natural (i.e., wild) equine behavior and the health of the equine gut microbiome and the impacts of human management. Full article

Objectives: Obesity disrupts adipose and systemic immune–metabolic homeostasis, yet the molecular mechanisms through which exercise restores abnormal tissue function remain incompletely defined. This study aimed to screen cross-tissue candidate genes associated with exercise-mediated correction of obesity-related transcriptional disorders via multi-tissue transcriptome profiling and bioinformatic gene prioritization. Methods: Transcriptomic datasets of mouse visceral white adipose, subcutaneous white adipose and skeletal muscle were downloaded from the public GEO database, covering normal control, high-fat induced obese and post-exercise intervention groups. R programming was applied to complete differential analysis, GO/KEGG enrichment, PPI network, LASSO and GSEA; independent human adipose datasets from GEO validated candidate genes. Results: Exercise reversed obesity-triggered transcriptional changes in adipose tissues. Exercise-responsive genes concentrated on immune inflammation, lipid and energy metabolism. Key hub genes for tissue remodeling were screened, and depot-specific pathway regulation was verified by GSEA. CCL2 showed consistent expression trends across mouse and human adipose data. Conclusions: This study identifies distinct tissue-specific transcriptional responses to exercise: visceral adipose mainly achieves reversal of obesity-induced inflammatory dysregulation, subcutaneous adipose undergoes combined immune–inflammatory and metabolic reprogramming, while skeletal muscle presents only energy-metabolism adaptive remodeling without obvious reversal of obese gene disorders. Immune–metabolic pathways dominate exercise-induced restoration in adipose tissues. Integrated network screening and cross-species validation identified CCL2 as a conserved candidate associated with exercise-responsive immune–metabolic pathways, providing valuable molecular candidates for further anti-obesity research. Full article

This study investigated the metabolic regulatory effects and underlying microbial mechanisms of Deinococcus radiodurans extract (DRE), using high-fat diet (HFD)-induced obese mice as the primary mechanistic model and naturally overweight felines. In the mouse model, a 1.5% DRE supplementation mitigated HFD-induced obesity, reduced serum total cholesterol and low-density lipoprotein levels, and markedly ameliorated hepatic steatosis. Fecal 16S rRNA gene sequencing revealed that DRE effectively reversed murine microbial dysbiosis by significantly restoring core commensals depleted by the HFD, notably Ureaplasma and the short-chain fatty acid (SCFA)-producer Odoribacter, while concurrently suppressing the overgrowth of obesity-associated taxa including Alloprevotella and Phascolarctobacterium. As a translational complement, a 28-day DRE intervention in felines under isocaloric maintenance conditions, with no significant change in body weight, body condition score, or fecal score, validated these systemic benefits, significantly enhancing serum total antioxidant capacity by 16.1% and reducing the systemic inflammatory marker serum amyloid A by 27.8%, indicating that the antioxidant and anti-inflammatory effects of DRE are independent of weight change. Concurrently, feline fecal microbiota profiling demonstrated a parallel ecological remodeling, characterized by the enrichment of potent SCFA producers (Oscillibacter and the [Eubacterium]_hallii_group) and the profound suppression of the pro-inflammatory pathogen Fusobacterium. Collectively, by integrating deep mechanistic insights from mice with translational evidence from felines, this study demonstrates that DRE exerts comprehensive anti-obesity and anti-inflammatory effects by regulating lipid metabolism and reshaping the gut microbiota, establishing its robust potential as a novel functional ingredient for metabolic health in companion animals. Full article