Metabolism open最新文献

{"title":"Association of hepatic steatosis with increased plasma xanthine oxidoreductase activity: MedCity21 health examination registry","authors":"Masafumi Kurajoh ,&nbsp;Shinya Fukumoto ,&nbsp;Seigo Akari ,&nbsp;Takashi Nakamura ,&nbsp;Yuya Miki ,&nbsp;Yuki Nagata ,&nbsp;Tomoaki Morioka ,&nbsp;Katsuhito Mori ,&nbsp;Yasuo Imanishi ,&nbsp;Toshio Watanabe ,&nbsp;Masanori Emoto","doi":"10.1016/j.metop.2025.100374","DOIUrl":"10.1016/j.metop.2025.100374","url":null,"abstract":"<div><h3>Background</h3><div>Steatotic liver disease, characterized by hepatic steatosis, increases the risk of metabolic and cardiovascular diseases. We previously reported that the plasma activity of xanthine oxidoreductase (XOR), primarily expressed in the human liver, is also associated with these diseases. The present study examined whether hepatic steatosis is associated with increased XOR activity.</div></div><div><h3>Methods</h3><div>This cross-sectional study included 334 participants who underwent health examinations and were not receiving urate-lowering or insulin therapy. Values for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) obtained with vibration-controlled transient elastography were used to assess hepatic steatosis and fibrosis. Plasma XOR activity was determined with our highly sensitive assay.</div></div><div><h3>Results</h3><div>Median CAP, LSM, and plasma XOR activity values were 234.0 dB/m, 3.6 kPa, and 27.2 pmol/h/mL, respectively. CAP was correlated with plasma XOR activity (ρ = 0.540, <em>P</em> &lt; 0.001) and subjects with hepatic steatosis (CAP ≥248 dB/m; n = 136) showed higher activity levels than those without (40.8 vs. 21.2 pmol/h/mL, <em>P</em> &lt; 0.001). Multivariable regression analyses, adjusted for confounding factors including aspartate aminotransferase, alanine aminotransferase, adiponectin, and homeostasis model assessment of insulin resistance (IR), indicated associations of CAP and hepatic steatosis with plasma XOR activity (β = 0.163, <em>P</em> &lt; 0.001; β = 0.086, <em>P</em> = 0.037, respectively). These associations remained consistent across subgroups stratified by alcohol consumption. Neither LSM nor hepatic fibrosis (LSM ≥7.9 kPa; n = 4) was associated with plasma XOR activity.</div></div><div><h3>Conclusions</h3><div>These results suggest that hepatic steatosis increases plasma XOR activity independent of liver enzymes, adiponectin, and IR.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100374"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Independent predictive role of nutritional markers in kidney function decline and mortality in diabetes","authors":"Tomohito Gohda ,&nbsp;Nozomu Kamei ,&nbsp;Marenao Tanaka ,&nbsp;Masato Furuhashi ,&nbsp;Tatsuya Sato ,&nbsp;Mitsunobu Kubota ,&nbsp;Michiyoshi Sanuki ,&nbsp;Risako Mikami ,&nbsp;Koji Mizutani ,&nbsp;Yusuke Suzuki ,&nbsp;Maki Murakoshi","doi":"10.1016/j.metop.2025.100386","DOIUrl":"10.1016/j.metop.2025.100386","url":null,"abstract":"<div><h3>Background</h3><div>Malnutrition and chronic inflammation are common in chronic kidney disease (CKD) and contribute to disease progression and mortality. While the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) scores assess nutritional status, their predictive values for CKD progression and mortality in individuals with diabetes, particularly independent of tumor necrosis factor receptor 2 (TNFR2), remains unclear. This study aimed to evaluate whether these markers predict outcomes beyond TNFR2.</div></div><div><h3>Subjects/methods</h3><div>We analyzed 640 individuals with diabetes, stratified by PNI quartiles (Q1 vs. Q2–4). Serum TNFR2 was measured using enzyme-linked immunosorbent assay. Nutritional status was assessed using PNI, GNRI, and CONUT scores. Cox proportional hazards models adjusted for covariates including TNFR2 examined associations between nutritional markers and a kidney event (≥30 % decline in estimated glomerular filtration rate), mortality, and a composite outcome.</div></div><div><h3>Results</h3><div>The mean age was 65 years; 53.9 % were male. Over median follow-ups of 5.3 and 5.4-years, 75 (11.7 %) experienced a kidney event and 44 (6.9 %) died. A total of 112 (17.5 %) experienced the composite outcome. All three markers were independently associated with a kidney event (PNI: hazard ratio [HR], 1.84; 95 % confidence interval [CI], 1.13–3.02) and a composite outcome (PNI: HR, 1.94; 95 % CI, 1.30–2.89). GNRI was the only marker independently associated with mortality (HR, 2.90; 95 % CI, 1.56–5.37).</div></div><div><h3>Conclusions</h3><div>PNI, GNRI, and CONUT scores strongly predict adverse outcomes in diabetes, emphasizing the importance of nutritional evaluation. Targeted nutritional interventions may improve prognosis.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100386"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harmonizing gut microbiota dysbiosis: Unveiling the influence of diet and lifestyle interventions","authors":"Sharvari S. Pandit ,&nbsp;Prabhu Meganathan ,&nbsp;Hemamalini Vedagiri","doi":"10.1016/j.metop.2025.100384","DOIUrl":"10.1016/j.metop.2025.100384","url":null,"abstract":"<div><div>The gut microbiota, comprising trillions of microorganisms inhabiting the gastrointestinal tract, is essential to human health and disease. Recent research has illuminated the interactions between many components of human physiology and the gut microbiota, including immune function, metabolism, and neurological health. Central to maintaining this symbiotic relationship is the concept of dysbiosis – an imbalance in the makeup and roles of the gut microbiota. Dysbiosis of the gut microbiota has emerged as a significant factor in the pathogenesis of numerous health conditions, spanning from gastrointestinal disorders like inflammatory bowel disease and irritable bowel syndrome to systemic diseases such as obesity, metabolic syndrome, and even neurological disorders like depression and anxiety. While dysbiosis can result from a myriad of factors including antibiotic use, stress, and genetic predispositions, emerging evidence suggests that diet and lifestyle choices exert profound influences regarding the make-up and capabilities of the gut microbiota. In this review, We explore the complex interactions among lifestyle, nutrition, and gut microbial dysbiosis. In particular, we investigate how the gut microbiota can be modified and dysbiosis can be mitigated by dietary patterns, food composition, prebiotics, probiotics, and lifestyle factors including exercise, stress reduction, and good sleep hygiene. Restoring microbial balance and enhancing general health and well-being can be achieved through preventive and therapeutic measures that can be made more effective by understanding how dietary and lifestyle changes might affect the gut microbiota. Through this exploration, we aim to elucidate the possibility of using lifestyle and dietary modifications as tools for managing gut microbial dysbiosis.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100384"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective serotonin reuptake inhibitors and glucose metabolism in Alzheimer's disease and related dementias: A systematic review and meta-analysis of brain metabolic and adverse event data","authors":"Faisal Alzenaidi ,&nbsp;Osama Aldoweesh ,&nbsp;Salman Alghofaili ,&nbsp;Abdulaziz Fadel ,&nbsp;Razan Ali Awad Lasloom ,&nbsp;Dhay Alharbi ,&nbsp;Faris Almalki ,&nbsp;Atheer Ahmad Alkhairi ,&nbsp;Maram Alharbi ,&nbsp;Norah Ahmed Alhamdan ,&nbsp;Ahmed Y. Azzam","doi":"10.1016/j.metop.2025.100389","DOIUrl":"10.1016/j.metop.2025.100389","url":null,"abstract":"<div><h3>Introduction</h3><div>Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression in Alzheimer's disease (AD), however their effects on glucose metabolism remain poorly understood. We conducted a systematic review and meta-analysis to evaluate SSRI effects on brain glucose metabolism and metabolic adverse events in AD patients.</div></div><div><h3>Methods</h3><div>Following PRISMA 2020 guidelines, we searched multiple databases up to July 11, 2025 for studies investigating SSRI effects on glucose-related outcomes in AD patients. Despite significant heterogeneity in study designs and populations, we performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. We performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. Advanced Bayesian hierarchical modeling and Markov simulations projected long-term metabolic outcomes.</div></div><div><h3>Results</h3><div>Twelve studies with total included 7143 participants met our inclusion criteria, including nine randomized controlled trials and three observational studies. Brain FDG-PET revealed SSRI use restored dorsal raphe nucleus hypometabolism (standardized mean difference 0.87, 95 % CI: 0.52–1.22, P-value = 0.001). Meta-analysis demonstrated increased gastrointestinal adverse events (risk ratio 2.15, 95 % CI: 1.68–2.76, P-value&lt;0.001, with moderate between-study heterogeneity), with sertraline showing highest rates. Citalopram 30 mg provided significant weight loss protection (risk ratio 0.13, 95 % CI: 0.02–0.98, P-value = 0.02), though this exceeds the recommended 20 mg maximum dose for elderly patients due to cardiac safety considerations. Long-term diabetes incidence showed no increased risk (hazard ratio 0.75, 95 % CI: 0.50–1.12, P-value = 0.15). Bayesian modeling revealed 85 % probability of beneficial brain metabolic effects and 89 % probability of citalopram superiority for weight protection.</div></div><div><h3>Conclusions</h3><div>SSRIs restore brain glucose metabolism in AD patients while causing manageable peripheral metabolic effects. Citalopram appears the best for weight-sensitive patients, while sertraline requires gastrointestinal monitoring. These findings support SSRI safety for metabolic outcomes in AD treatment, however longer-term studies with controlled metabolic outcomes are needed to confirm our findings. The observed citalopram weight protection benefit was documented at 30 mg daily, which exceeds recommended dosing limits for elderly patients due to cardiac safety concerns.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100389"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative lipidomic analysis reveals distinct metabolic traits between stromal cell subpopulations in human orbital adipose tissue","authors":"Shuwei Tian ,&nbsp;Xiaoli Zhang ,&nbsp;Jiayong Yu ,&nbsp;Juan Cai ,&nbsp;Danni Wei ,&nbsp;Siqi Li ,&nbsp;Pengfei Cai ,&nbsp;Wei Song ,&nbsp;Suihan Feng ,&nbsp;Mengle Shao ,&nbsp;Haizhou Li","doi":"10.1016/j.metop.2025.100380","DOIUrl":"10.1016/j.metop.2025.100380","url":null,"abstract":"<div><div>Adipose tissue, a pivotal metabolic regulator, houses diverse stromal cell populations influencing its dynamic functions. Recent omics studies, including transcriptomics and proteomics, have revealed intricate cellular heterogeneity, yet comprehensive metabolic profiling remains limited. Leveraging fluorescence-activated cell sorting (FACS), we isolated PDGFRα+ DPP4+ and PDGFRα+ DPP4- adipose stromal cells (ASCs) from human orbital adipose tissue (OAT). Integrating gene expression analysis, in vitro adipogenesis assays, and quantitative lipidomics, we characterized their functional and metabolic distinctions. DPP4- ASCs exhibited enhanced adipogenic potential and distinct lipidomic profiles, featuring elevated ceramides and triacylglycerols compared to DPP4+ ASCs. Differential gene expression highlighted metabolic and adipogenic gene signatures reflective of their functional roles in adipose tissue remodeling. Our findings underscore the metabolic heterogeneity within OAT stromal fibroblasts, implicating DPP4- ASCs as potent regulators of adipogenesis and metabolic homeostasis. These insights enhance our understanding of adipose tissue plasticity and may inform therapeutic strategies for conditions like thyroid-associated ophthalmopathy.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100380"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D3 supplementation in women practicing orthodox religious and intermittent fasting: A controlled study with formulation-specific effects","authors":"Spyridon N. Karras ,&nbsp;Konstantinos Michalakis ,&nbsp;Maria Kypraiou ,&nbsp;Antonios Vlastos ,&nbsp;Marios Anemoulis ,&nbsp;Georgios Koukoulis ,&nbsp;Zadalla Mouslech ,&nbsp;Filotas Talidis ,&nbsp;Costas Haitoglou ,&nbsp;Evangelos G. Papanikolaou ,&nbsp;Neoklis Georgopoulos ,&nbsp;Georgios Tzimagiorgis","doi":"10.1016/j.metop.2025.100391","DOIUrl":"10.1016/j.metop.2025.100391","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin D deficiency is prevalent among monastic Orthodox populations, likely due to their sartorial habits and religious fasting rules. Data on supplementation in similar populations are lacking, including responses in restoring vitamin D sufficiency and to specific formulations of vitamin D supplements. This controlled study evaluated the efficacy of a daily oral vitamin D regimen, using oil-based drops and tablets, in restoring vitamin D status in a population of Orthodox nuns from Northern Greece, as well as assessing potential formulation-specific effects in the context of vitamin D supplementation.</div></div><div><h3>Methods</h3><div>A total of 41 Orthodox nuns practicing intermittent fasting received a daily dose of 2.500 IU vitamin D3 in either oil-based drops or tablets for 16 weeks and were compared to 40 matched controls without supplementation. Serum concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), calcium, and albumin were measured at baseline and after 16 weeks in both groups.</div></div><div><h3>Results</h3><div>In the supplemented group, mean serum 25(OH)D concentrations increased significantly from 21.44 ± 9.08 ng/mL to 34.27 ± 10.33 ng/mL (p = 0.022), while PTH decreased from 66.18 ± 21.31 pg/mL to 50.71 ± 15.92 pg/mL (p = 0.018). The control group showed no significant changes in either 25(OH)D (23.90 ± 7.11 vs. 26.53 ± 9.14 ng/mL, p = 0.067) or PTH (41.75 ± 15.74 vs. 40.11 ± 13.56 pg/mL, p = 0.415). Multivariate regression—adjusting for baseline 25(OH)D, BMI, and body fat percentage—indicated that the form of supplementation (tablet vs. drops) was not an independent predictor of the change in vitamin D concentrations (β = +2.77, p = 0.456). The only statistically significant predictor was baseline 25(OH)D (β = −0.63, p &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>A daily regimen of oral vitamin D3, administered as either drops or tablets, is effective in significantly improving vitamin D status and reducing PTH concentrations in women adhering to intermittent fasting religious practices. These findings support targeted supplementation strategies in at-risk fasting populations, particularly those with vitamin D deficiency, regardless of the form of oral supplementation.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100391"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity: Prevalence, causes, consequences, management, preventive strategies and future research directions","authors":"Sirwan Khalid Ahmed,&nbsp;Ribwar Arsalan Mohammed","doi":"10.1016/j.metop.2025.100375","DOIUrl":"10.1016/j.metop.2025.100375","url":null,"abstract":"<div><div>Obesity has emerged as one of the most pressing global public health challenges of the 21st century. Obesity has reached epidemic proportions worldwide, with over 1 billion people classified as obese in 2022, representing 13 % of the global population. Since 1975, obesity rates have tripled, and projections indicate that by 2035, around 1.9 billion adults—approximately 25 % of the world's population—will be affected. Looking further ahead to 2050, it is estimated that 3.80 billion adults, representing more than half of the anticipated global adult population, will be living with overweight or obesity. The increasing burden of obesity is associated with an alarming rise in non-communicable diseases, including type 2 diabetes, cardiovascular diseases, and multiple cancers, collectively contributing to over 5 million deaths annually. Obesity is driven by complex interactions between genetic, behavioral, environmental, and socioeconomic factors, with rapid urbanization and globalization accelerating the consumption of high-calorie diets and sedentary lifestyles. While historically prevalent in high-income nations, obesity rates are now rising most rapidly in low- and middle-income countries (LMICs), with over 70 % of obese individuals living in developing nations. The economic costs of obesity are staggering, with projections estimating a global financial burden of $4.32 trillion per year by 2035, equivalent to 3 % of the global GDP. This article explores the epidemiology, determinants, health implications, and policy responses to obesity, emphasizing the urgent need for multisectoral strategies to mitigate its impact. Public health initiatives, taxation on sugar-sweetened beverages, improved food regulations, and increased physical activity promotion are essential components of evidence-based interventions. Addressing the obesity crisis requires global cooperation to implement sustainable, long-term strategies targeting both prevention and treatment.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100375"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supplementary use of natural products in managing dumping syndrome: Exploring dietary and phytochemical interventions","authors":"Abdullah Al Lawati ,&nbsp;Ayman N. Alhabsi ,&nbsp;Ali Al Sabti ,&nbsp;Raksha S. Krishnan ,&nbsp;Sulaiman Alkindi ,&nbsp;Srijit Das ,&nbsp;Mohammed Al-Abri","doi":"10.1016/j.metop.2025.100387","DOIUrl":"10.1016/j.metop.2025.100387","url":null,"abstract":"<div><div>Dumping syndrome (DS) is a known complication following bariatric surgery, caused by rapid gastric emptying into the small intestine. It presents in two forms: early dumping, with gastrointestinal and vasomotor symptoms occurring within 30–60 min after meals; and late dumping, which arises 1–3 h postprandially due to reactive hypoglycaemia. Standard management includes dietary changes and medications, but tolerability and long-term efficacy are variable. Recently, interest has grown in using natural products and nutritional compounds as adjuncts or alternatives. Fibre-rich foods, sugar substitutes, and medicinal plants may delay gastric emptying, reduce glucose spikes, or modulate gut hormones such as GLP-1 and GIP. Several phytochemicals, polyphenols, flavonoids, alkaloids, and terpenoids have demonstrated promise in reducing DS symptoms, especially in late dumping. Functional foods may enhance satiety, slow carbohydrate absorption, and improve glycaemic control. Although most data are from preclinical or limited clinical studies, natural compounds appear to be well-tolerated and safe, offering potential advantages over standard pharmacological agents. This review summarises emerging evidence on the role of natural products in managing DS, their mechanisms of action, and their clinical relevance in post-bariatric care. The findings aim to support translational metabolic care and provide practical guidance for clinicians and dietitians managing DS in diverse patient populations.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100387"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fat diet may increase the risk of insulin resistance by inducing dysbiosis","authors":"Ebrahim Abbasi,&nbsp;Iraj Khodadadi","doi":"10.1016/j.metop.2025.100381","DOIUrl":"10.1016/j.metop.2025.100381","url":null,"abstract":"<div><div>High-fat diet (HFD) poses various health risks, such as obesity, insulin resistance (IR), fatty liver, gut microbiota dysbiosis, cognitive impairment, inflammation, and oxidative stress. HFD can alter gastrointestinal function and structure, resulting in changes of the intestinal mucosa, gastric secretions, intestinal connective tissue, intestinal motility, intestinal metabolomics profiles, and intestinal microbiota. The intestine and its microbiota process nutrients and produce molecules that can regulate insulin action and secretion. Changes in the gut microbiome (dysbiosis) and their products may have long-term effects that are not fully understood. Gut microbiota have long been documented to induce metabolic endotoxemia by releasing lipopolysaccharide, which causes systemic inflammation and insulin resistance (IR). HFD may has direct roles in the development of insulin resistance (IR). HFD can induce dysbiosis by reducing SCFAs and decreasing the activation of free fatty acid receptors (FFARs). Furthermore, HFD can increase the activation of the toll-like receptor (TLR) pathway. Hence, HFD by inducing inflammation, oxidative stress, endotoxemia, and hyperglycemia can increase the risk of IR. Therefore, this review aims to delineate the role of gut microbiota directly or indirectly involved in HFD-induced IR. These findings may clarify valuable preventive and therapeutic targets for countermeasures to IR in people who use the Western diet.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100381"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celastrol targets CKB-mediated futile creatine cycle in human brown adipocytes thermogenesis","authors":"Jingyi Ni ,&nbsp;Baicheng Wang ,&nbsp;Xinyue Liu ,&nbsp;Rui Yin ,&nbsp;Jinlin Tang ,&nbsp;Siyu Hua ,&nbsp;Xiaoxiao Zhang ,&nbsp;Yangyang Wu ,&nbsp;Shihu Zhang ,&nbsp;Chenbo Ji","doi":"10.1016/j.metop.2025.100359","DOIUrl":"10.1016/j.metop.2025.100359","url":null,"abstract":"<div><div>Celastrol is widely recognized as one of the most potent anti-obesity agents, and its ability to promote adipocyte thermogenesis is thought to be a key mechanism. However, the precise molecular targets through which celastrol modulates thermogenesis in human adipocytes remain unclear. In this study, we synthesized a celastrol-based small molecular probe and employed a combination of photoaffinity labeling (PAL), click chemistry, and Surface Plasmon Resonance (SPR) to identify its direct binding targets. Our results reveal that celastrol directly interacts with creatine kinase B-type (CKB), leading to an increase in CKB protein stability. This suggests that celastrol modulates the futile creatine cycle within human brown adipocytes, thereby contributing to thermogenesis. Collectively, our findings provide new insights into the molecular mechanisms by which celastrol promotes thermogenesis in human brown adipocytes. Notably, we demonstrated that celastrol targets CKB-mediated futile creatine cycle for the first time. These findings not only deepen our understanding of celastrol's role in weight loss but also provides a potential strategy for obesity treatment.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100359"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143685345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}