Search Results (8,863)

Background: Cardiometabolic risk (CMR), including obesity, dyslipidemia, hypertension, and impaired glucose regulation, disproportionately affects Hispanic/Latinx adults in the United States (U.S.). Although plant-forward dietary patterns are established as cardioprotective, less is known about how dietary patterns within Hispanic/Latinx subgroups relate to CMR. Methods: A narrative review was conducted of observational studies among U.S. Hispanic/Latinx adults (≥18 years) examining defined dietary patterns (a priori, a posteriori, or hybrid) in relation to CMR outcomes (e.g., BMI, waist circumference, blood pressure, glucose, lipids). Risk of bias was assessed using an adapted version of the Newcastle–Ottawa Scale. Results: Ten studies met the inclusion criteria, including Seventh-day Adventist Latinx, Puerto Rican adults, Mexican American adults, Hispanic women, and a national Hispanic cohort. Plant-forward dietary patterns were associated with lower BMI and waist circumference, lower triglycerides and fasting glucose, and higher HDL-C. In contrast, energy-dense patterns characterized by refined grains, added sugars, processed meats, fried foods, solid fats, and sugar-sweetened beverages were associated with greater adiposity, poorer lipid profiles, and higher blood pressure. Traditional rice-and-beans–based patterns observed in Puerto Rican and Mexican American groups were associated with central adiposity and higher metabolic syndrome prevalence, despite modestly higher intakes of fruits, vegetables, and fiber. Study quality ranged from good (n = 4) to very good (n = 6). Conclusions: Across Hispanic/Latinx subgroups, plant-forward dietary patterns were associated with favorable cardiometabolic profiles, whereas refined and animal-based patterns aligned with higher CMR. Given the predominance of cross-sectional evidence, these findings should be interpreted as associative rather than causal. Culturally grounded dietary counseling, along with additional longitudinal and intervention studies, is needed to support cardiometabolic health in these populations. Full article

This study intends to assess oxidative stress markers and endogenous enzymes in plasma and peritumoral adipose tissues (PATs) obtained from normal subjects and patients with stages I-IV colorectal cancer (CRC). 63 participants were recruited, including 23 patients with colorectal cancer and 40 healthy subjects. CRC patients had increased circulating malondialdehyde (MDA) and protein carbonyl concentrations, as well as reduced superoxide dismutase (SOD) and catalase activities, compared to normal volunteers. (p < 0.05). The findings aligned with the oxidative parameters assessed in peritumoral adipose tissue. Superoxide production in PAT was dramatically higher in the CRC group compared to the control group (p < 0.05). Moreover, oxidative stress markers were progressively altered in relation to CRC stages. Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) protein expression was reduced in PAT isolated from CRC compared to normal subjects and associated with CRC stages. CRC patients showed a systemic and peritumoral oxidative imbalance, along with elevated superoxide production in the PAT. The oxidative modifications worsened with the progression of CRC stage and were associated with the downregulation of the Nrf2/HO-1 antioxidant cascade in peritumoral adipose tissue. Full article

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic low-grade inflammation. The NLRP3 inflammasome has been implicated in various inflammatory conditions, but its role in PCOS remains unclear. This study aimed to investigate whether the NLRP3 inflammasome and its associated components, IL-1β, CASP-1, and PYCARD, are involved in the pathogenesis of PCOS. Gene and protein expression levels of NLRP3, IL-1β, CASP-1, and PYCARD were assessed in adipose tissue samples (visceral and subcutaneous) from women with and without PCOS using qPCR and Western blotting. Contrary to our initial hypothesis, CASP-1 gene expression was significantly higher in non-PCOS participants across all adipose depots examined. Similarly, NLRP3 protein levels were significantly upregulated in visceral adipose tissue (VAT) and in combined adipose samples from the non-PCOS group. No significant group differences were observed in the gene expression of NLRP3, IL-1β, or PYCARD. These findings suggest a more complex role for the NLRP3 inflammasome in PCOS than previously assumed. The elevated CASP-1 and NLRP3 levels in non-PCOS participants may reflect compensatory regulation, subclinical inflammation in controls, or technical variability. Further research is needed to explore alternative inflammasome pathways and the influence of metabolic factors, such as insulin, on inflammasome regulation in PCOS. Full article

Epicardial adipose tissue (EAT) function may influence the heart, given its metabolic actions and proximity to the heart. We hypothesized that diabetes mellitus (DM) alters miRNA expression across adipose tissue types, and that modifications in EAT may have critical implications for cardiac physiology. To test this, we compared EAT and subcutaneous adipose tissue (SAT) miRNA profiles between patients with and without DM and across tissues within each disease group. Paired biopsies from patients with (n = 18) and without DM (n = 46) undergoing cardiac surgery were analyzed using miRNA profiling and bioinformatics. Among 680 miRNAs screened, 34 were uniquely expressed in EAT, confirming a distinct molecular signature in this fat depot. Notably, miR-155-5p was significantly elevated in EAT from patients with DM, indicating a localized metabolic effect. In SAT, miR-93-3p and miR-223-3p were upregulated in patients with DM and consistently higher than in EAT, regardless of DM status, indicating tissue-specific regulation. miR-324-5p was more expressed in SAT of patients in the NDM group, reflecting combined effects of tissue type and DM. These patterns remained consistent across cardiac disease stratifications. Pathway analysis revealed that miRNAs enriched in EAT target genes involved in cardiomyocyte growth and differentiation. Overall, the findings highlight the unique miRNA profile of epicardial fat and its altered response to DM, supporting its relevance in cardiac physiology. Full article

Background/Objectives: A number of initiatives have refocused attention from obesity to adiposity-related organ dysfunction. In this prospective observational study, we examined this paradigm postpartum. Methods: At King’s College Hospital, London, UK, we invited for review by six months postpartum, consecutive women with GDM (N = 1442, September 2023–August 2025) and without GDM (N = 646, January 2025–August 2025). Those with excess adiposity (BMI ≥ 30 kg/m² and waist-to-height ratio > 0.5) were assessed for organ dysfunction, using criteria from a recent Commission: anovulation, metabolism or renal clusters, raised blood pressure, or elevated end-diastolic left ventricular filling pressure. Multiple regression determined predictors of adiposity-related organ dysfunction, the prevalence of which was calculated as a range (highest estimate: absolute organ dysfunction prevalence; lowest estimate: adiposity-adjusted, as highest estimate minus prevalence of organ dysfunction in women without excess adiposity). Results: Of those invited for review, 1086/1442 (75.3%) GDM and 562/646 (87.0%) non-GDM women attended, at median 5.8 months after birth (interquartile range 4.8–6.7). Excess adiposity was observed in 385/1086 (35.5%) GDM and 117/562 (20.8%) non-GDM women, among whom organ dysfunction was seen in 61.0% GDM (235/385), 51.3% non-GDM (60/117). 35.9% (408/1137) of women without excess adiposity. Organ dysfunction attributable to excess adiposity was estimated to be 22.9% (58.8% minus 35.9%), and was poorly predicted by the multivariable model (AUC 0.64, 95%CI 0.60–0.69). Conclusions: Among women with prior GDM, organ dysfunction attributable to excess adiposity affects at least 20% of those with excess adiposity postpartum, and is not currently predictable. Full article

Background/objectives: Metabolic abnormalities, independent of excess weight, may contribute to cancer risk even among individuals of normal weight, though their role remains unclear. This study sought to ascertain if metabolically unhealthy normal-weight (MUNW) individuals, generally characterized by a normal body mass index alongside the presence of metabolic abnormalities, have higher cancer risk than metabolically healthy peers, to analyze variations in risk across obesity-related cancer types, and to examine which single specific metabolic components can predict cancer independently in normal-weight individuals. Methods: Two authors systematically searched the PubMed, EMBASE, and Web of Science databases for longitudinal studies, published from inception to July 2025, that included normal-weight adults, classified participants by metabolic health status, and reported incident cancer outcomes in metabolically unhealthy versus healthy normal-weight groups. Hazard ratio (HR) estimates were extracted from each study and were pooled using random-effects inverse-variance model with empirical Bayes variance estimator. Results: Thirty-five studies involving 18,210,858 participants (56.0% females, mean age = 53.8 years) were included. A total of 280,828 new cancer cases were diagnosed during follow-up (mean = 10.6 years). In comparison with metabolically healthy normal-weight individuals, MUNW individuals had a 20% higher risk of cancer (HR = 1.20, 95% confidence interval [CI]: 1.13–1.28). Increased risks were observed for gastric cancer (HR = 1.40, 95% CI: 1.04–1.87), pancreatic cancer (HR = 1.37, 95% CI: 1.21–1.54), and colorectal cancer (HR = 1.34, 95% CI: 1.14–1.57), which were the cancer types showing statistically significant associations in subgroup analyses. Normal-weight participants presenting specific metabolic factors like central adiposity or glucose metabolism abnormalities had a 20% (HR = 1.20, 95% CI: 1.13–1.37) and 23% (HR = 1.23, 95% CI: 1.06–1.41) increased cancer risk, respectively. Conclusions: MUNW individuals are at higher risk of cancer, with specific metabolic abnormalities, particularly central adiposity and impaired glucose regulation, emerging as the factors most strongly associated with increased risk in normal-weight individuals. Routine metabolic screening and detailed phenotyping are crucial to identify these risks. Full article

Adiposity-Based Chronic Disease (ABCD) is known to increase the risk of aggressive prostate cancer (PCa), recurrent disease after treatment for localized PCa, and PCa mortality. A key mechanistic link contributing to this enhanced risk is chronic inflammation originating from excess white visceral adipose tissue (WAT; VAT) and periprostatic adipose tissue (ppWAT). Contributing to systemic inflammation is gut dysbiosis, which itself may be caused by ABCD as well as background local inflammation (prostatitis), which is common in aging men and may be exacerbated by the urinary microbiome. Investigating the molecular biology driving inflammation and its association with increased PCa risk, a recent paper applied a network and gene set enrichment to adipokine drivers in the ABCD-PCa network. It found prominent roles for MCP-1, IL-1β, and CXCL-1 in addition to confirming the importance of exposure to lipopolysaccharides and bacterial components, corroborating the role of gut dysbiosis. To further unravel the mechanistic links between ABCD and PCa risk, this critical review will discuss the current literature on prominent inflammatory signaling pathways activated in ABCD; the influence of gut dysbiosis, the urinary microbiome, and chronic prostatitis; and current hypotheses on how these domains may result in the development of aggressive PCa over a man’s life. Moreover, we performed a novel pathway enrichment analysis to further evaluate the associations between ABCD, PCa risk, gut dysbiosis, and the prostate microbiome, the results of which were partitioned into extracellular and intracellular signaling pathways. In the extracellular space, novel mechanistic links between gut dysbiosis and MCP-1, IL-1β, CXCL1, and leptin via bacterial pathogen signaling and the intestinal immune network (for IgA production), crucial for gut immune homeostasis, were found. Within the intracellular space, there were downstream signals activating chemokine and type 2 interferon pathways, focal adhesion PI3K/Akt/mTOR pathways, as well as the JAK/STAT, NF-κB, and PI3K/Akt pathways. Overall, these findings point to an emerging molecular pathway for PCa oncogenesis influenced by ABCD, gut dysbiosis, and inflammation, and further research, possibly with lifestyle program-based clinical trials, may discover novel biomarker panels and molecular targeted therapies for the prevention and treatment of PCa. Full article

Background: The belief that “sugar feeds cancer” is widespread and has strongly influenced public perceptions, patient behavior, and dietary recommendations, despite uncertainty regarding its scientific validity. This belief largely stems from misinterpretation of the Warburg effect, which describes altered glucose metabolism in cancer cells rather than dietary sugar dependence. The objective of this review was to critically evaluate whether dietary sugar intake directly contributes to cancer development or progression by examining the totality of epidemiological, experimental, and mechanistic evidence. Methods: We conducted a narrative review of human epidemiological studies, experimental animal and cell-based models, and mechanistic investigations published between 1980 and July 2025. Evidence was synthesized across cancer types, sugar sources, and biological pathways, with careful consideration of study design, exposure relevance, and key confounders, including obesity, insulin resistance, and overall dietary patterns. Results: Across cancer types, epidemiological evidence showed predominantly null or inconsistent associations between sugar intake and cancer risk or outcomes, with positive findings largely confined to metabolically susceptible subgroups and often attenuated after adjustment for adiposity and energy intake. Experimental studies suggested potential tumor-promoting effects under non-physiological conditions, while mechanistic data indicated that sugar influences cancer risk indirectly through insulin signaling, inflammation, and metabolic dysfunction rather than direct tumor fueling. Conclusions: Current evidence does not support the hypothesis that dietary sugar directly “feeds” cancer in humans. Overemphasis on sugar avoidance risks nutritional and psychological harm, particularly among cancer patients. Evidence-based guidance should prioritize overall dietary quality, metabolic health, and patient well-being rather than isolated sugar restriction. Full article

Osteoarthritis (OA) is the most common multifactorial joint disease characterized by progressive cartilage degradation and impaired tissue repair. Osteochondral defects represent a major clinical challenge within OA, as damage to cartilage and underlying bone can initiate degenerative changes and contribute to joint deterioration. The Wnt/β-catenin signaling pathway plays an important role in OA pathogenesis, and its dysregulation contributes to chondrocyte catabolism and cartilage loss. NOTUM, an extracellular Wnt inhibitor, has emerged as a potential therapeutic modulator capable of restoring signaling balance and promoting cartilage homeostasis. This study aimed to evaluate the efficacy of NOTUM compared with hyaluronic acid (HA), human adipose-derived mesenchymal stromal cells (hAd-MSCs), and Colchicine in a rabbit osteochondral defect model relevant to osteoarthritis. Twenty-seven New Zealand White rabbits underwent standardized femoral condyle injury and received single-dose treatments. Serum levels of cartilage biomarkers—Procollagen Type IIA N-terminal Propeptide (PIIANP) and Cartilage Oligomeric Matrix Protein (COMP)—were measured by ELISA at 4, 6, and 8 weeks post-surgery, and histological repair at week 12 was assessed using the modified O’Driscoll scoring system. NOTUM treatment significantly increased PIIANP and decreased COMP levels compared with HA, indicating enhanced cartilage synthesis and reduced degradation. Histological scores confirmed superior surface morphology and tissue composition in NOTUM-treated joints. These findings suggest that NOTUM performs a protective and regenerative effect through Wnt/β-catenin modulation, supporting the conclusion that it enhances osteochondral defect repair and motivating further studies of NOTUM as an OA therapy. Full article

Background/Objectives: Pancreatic cancer is among the most aggressive malignancies, with poor survival rates. Emerging evidence suggests that body composition, including skeletal muscle mass and adiposity distribution, plays a crucial role in predicting patient outcomes. However, its impact on survival in pancreatic cancer remains incompletely understood. The aim of this systematic review was to assess the correlation between body composition parameters and survival outcomes in pancreatic cancer patients, focusing on overall survival. Methods: A comprehensive literature search was conducted, including three main components: pancreatic cancer, body composition, and survival outcomes. Results: 23 studies were included in this review. The findings indicate that body composition can serve as a predictor of survival in pancreatic cancer patients, with 21 studies reporting a significant correlation. The most frequently observed predictor, with 11 studies reporting, was not a baseline parameter but rather changes in parameters over time during treatment. However, discrepancies remain regarding the extent of predictive power and the relative importance of individual components. Conclusions: Specific body composition parameters hold potential as prognostic indicators of survival in pancreatic cancer patients. However, further research is necessary to establish consistent patterns and to clarify which parameters are most predictive and under what conditions. Full article

Obesity treatments increasingly target multiple pathways beyond appetite suppression. We evaluated KBN2202, a salicylate-derived small molecule, in a high-fat diet (60% kcal from fat) mouse model using female and male C57BL/6J mice treated for 8 weeks with oral KBN2202 (20 mg/kg/day) or a matched-volume vehicle (1% DMSO/PBS). Body weight was recorded weekly, and food intake was measured daily; serum hormones and cytokines, adipose tissue histology, and open-field behavior were assessed at the end of the study. Under our experimental conditions, HFD increased body weight and gonadal white adipose tissue (gWAT)/brown adipose tissue (BAT) mass in females, whereas males showed only modest HFD-associated weight gain and did not develop a clear obesity phenotype. KBN2202 significantly reduced peri-ovarian gWAT mass and adipocyte size without altering overall body weight. In females, circulating glucagon-like peptide-1 (GLP-1) increased, uncoupling protein 1 (UCP1) in gWAT showed a non-significant upward trend, and serum TNF-α was selectively decreased, while MCP-1 and IL-1β were unchanged. Locomotor activity was unaltered, and anxiety-like behavior was reduced. Male mice did not show comparable adipose effects. These findings indicate depot-specific, peripheral modulation of adipose remodeling, hormonal balance, and inflammatory tone by KBN2202, supporting its further investigation as an adipose-targeted metabolic modulator complementary to incretin-based therapies. Full article

Lipodystrophies are rare syndromes characterized by partial or complete loss of subcutaneous adipose tissue leading to ectopic lipid deposition, insulin resistance, and the same metabolic derangements observed in obesity. Given the role of gut microbiota in metabolic disorders, we investigated whether its signature in obesity may be mirrored by that found in lipodystrophies, possibly contributing to their overlapping metabolic abnormalities. In this cross-sectional study, we included 8 individuals with lipodystrophy (LD), 16 individuals with obesity (Ob)—further categorized into 8 metabolically healthy (MHO) and 8 metabolically unhealthy (MUHO)—and 16 normal-weight controls (N). We assessed clinical and metabolic characteristics and performed 16S rRNA sequencing and bioinformatic analyses on fecal samples to characterize the gut microbiome. LD presented significantly lower body mass index (BMI) and waist circumference than Ob, but, from a metabolic perspective, LD showed similarity with MUHO and presented significantly lower levels of HDL-C and higher triglycerides compared to both N and MHO. Gut microbiota analysis revealed reduced α-diversity in LD, MHO and MUHO compared to N, whilst β-diversity and Firmicutes/Bacteroidetes ratio differences were not significant. At the phylum level, differential abundance analysis revealed that LD individuals exhibit similar microbial characteristics to MUHO and higher Verrucomicrobiota levels compared to MHO. The shared gut microbiota signature suggests another potential unexplored link between the pathogenesis of metabolic complications in lipodystrophies and obesity, providing novel insights into the complex interplay between dysbiosis and adiposopathy. Larger longitudinal studies are needed to explore the role of specific taxa and for a more precise characterization of different lipodystrophy subtypes. Full article

Obesity, sarcopenia, and heart failure with preserved ejection fraction (HFpEF) constitute an interconnected clinical triad driven by multisystem mechanisms centered on the adipokine axis. Adipose tissue, now recognized as a dynamic endocrine organ, undergoes pathological remodeling in obesity, characterized by hypoxia, chronic low-grade inflammation, and dysregulated adipokine secretion. These changes impair endothelial function, promote myocardial fibrosis, and disrupt skeletal muscle metabolism, thereby linking cardiometabolic and musculoskeletal dysfunction. This review integrates current evidence on homeostatic adipokines, such as adiponectin, apelin, and omentin, that preserve vascular and muscular resilience, as well as stress-inducible adipokines, such as leptin, resistin, and GDF15, that reflect or amplify metabolic and inflammatory injury. A maladaptive adipokine milieu associates with a self-reinforcing cycle of endothelial dysfunction, myocardial stiffening, and muscle atrophy that characterizes s HFpEF in the context of obesity and sarcopenia. We further discuss emerging translational applications, including diagnostic and prognostic adipokine signatures, targeted modulation of adipokine pathways, and the therapeutic impact of GLP-1 receptor agonists on adipose–cardiovascular–muscle crosstalk. Remaining challenges, including the adiponectin paradox and pleiotropic adipokine effects, highlight the need for precision-medicine approaches integrating multimodal biomarker profiling with cardiometabolic and musculoskeletal phenotyping. Full article

Background/Objectives: Preoperative body composition has been implicated as a factor affecting clinical outcomes in several types of cancer. However, there is limited evidence regarding whether preoperative body composition can predict the prognosis following gastrectomy for gastric cancer (GC). We aimed to investigate the role of preoperative body composition as a prognostic factor for overall survival (OS) and relapse-free survival (RFS) after gastrectomy for GC. Methods: This prospective study included 540 patients who underwent gastrectomy for GC at the Kanagawa Cancer Center, Japan, between December 2013 and November 2017. Preoperative body composition was assessed using the skeletal muscle index and visceral adipose tissue area derived from computed tomography scans. Patients were classified into four groups: non-sarcopenic non-obesity (NN), sarcopenic non-obesity (SN), non-sarcopenic obesity (NO), and sarcopenic obesity (SO). Results: A total of 448 patients (NN, 184; SN, 52; NO, 186; SO, 26) were included in the final analysis. In terms of OS, the SO group showed significantly worse survival than the NN group (72.1% vs. 87.6%, p = 0.01). Similarly, regarding RFS, the SO group had significantly worse outcomes than the NN group (68.4% vs. 86.2%, p = 0.007). Multivariate analysis identified SO as an independent risk factor for both OS (hazard ratio [HR], 3.18; 95% confidence interval [CI], 1.33–7.64; p = 0.01) and RFS (HR, 3.08; 95% CI, 1.36–6.95; p = 0.01). Conclusions: Preoperative SO was associated with poorer outcomes in patients undergoing gastrectomy for GC. Full article

Obesity and metabolic disorders are an increasing concern in companion animals, creating demand for herb-derived nutraceuticals and functional feeds. This study evaluated whether a water extract of Aster pekinensis (AP) ameliorates high-fat-diet (HFD)-induced obesity and metabolic dysfunction in mice. The phytochemical profile of AP was characterized by mass spectrometry, revealing oleanane-type triterpenoid saponins and dicaffeoylquinic acids. Male C57BL/6 mice were fed an HFD and orally given AP (10–200 mg/kg/day) for 12 weeks, with normal diet and untreated HFD groups as controls. AP at 50–200 mg/kg/day reduced body-weight gain, adipose tissue mass and food efficiency without lowering food intake, and improved fasting glucose and atherogenic lipid indices. AP also enhanced glucose tolerance and insulin sensitivity, attenuated hepatic steatosis, hepatocellular ballooning, lobular inflammation and non-alcoholic fatty liver disease (NAFLD) Activity Score, and decreased serum liver enzyme activities. These effects were accompanied by modulation of hepatic genes involved in lipogenesis and inflammation. Together, these findings indicate that AP extract mitigates diet-induced obesity and NAFLD-like liver injury and supports further development as a herb-derived nutraceutical or functional feed ingredient for managing obesity-related metabolic disorders in companion animals. Full article