npj Metabolic Health and Disease最新文献

The clock gene cycle synchronizes circadian metabolic oscillations uniquely in reproductively active Culex pipiens females. 时钟基因周期在繁殖活跃的雌性库蚊中独特地同步昼夜代谢振荡。

npj Metabolic Health and Disease Pub Date : 2026-10-06 DOI: 10.1038/s44324-026-00136-y

Mizuki Yoshida, Matthew E Wolkoff, Cheolho Sim, Megan E Meuti, Matthias S Klein

{"title":"The clock gene cycle synchronizes circadian metabolic oscillations uniquely in reproductively active Culex pipiens females.","authors":"Mizuki Yoshida, Matthew E Wolkoff, Cheolho Sim, Megan E Meuti, Matthias S Klein","doi":"10.1038/s44324-026-00136-y","DOIUrl":"10.1038/s44324-026-00136-y","url":null,"abstract":"The circadian clock regulates changes in daily metabolite abundance, coordinating animal activity, feeding and rest. The Northern house mosquito, Culex pipiens, also displays seasonal changes between periods of reproductive activity and overwintering diapause, regulated by changes in daylength. However, differences in metabolic oscillations between diapause and non-diapause have yet to be characterized. We hypothesized that reproductively active, non-diapausing mosquitoes would show large metabolic oscillations compared to diapausing mosquitoes. Our previous work demonstrated that CYCLE regulates insulin signaling, reproductive growth and olfaction, and that knocking out cycle causes a diapause-like state regardless of photoperiod, thus we predicted large-scale disruptions to the daily and seasonal metabolomes of CpCyc-/- mosquitoes. We identified 27 metabolites showing highly synchronized oscillations in non-diapausing wildtype (WT) females, but only 11 oscillating metabolites in WT diapausing females. We also observed large-scale metabolic disruptions in CpCyc-/- females reared under both long and short days, especially a loss of synchronicity between oscillations. This is the first report on differences in oscillating metabolites between diapausing and non-diapausing Cx. pipiens, and the impact of cycle on oscillating metabolites. This provides additional mechanistic insights as to how the circadian clock regulates daily and seasonal metabolic differences, with implications for insulin dysregulation and metabolic disorders.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121903","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}

引用次数: 0

A digital twin for tracking and forecasting glycemia with septic patients in ICUs. 重症监护室脓毒症患者血糖跟踪和预测的数字双胞胎。

npj Metabolic Health and Disease Pub Date : 2026-10-01 DOI: 10.1038/s44324-026-00132-2

Xiang Cao, Chao Cai, Jianguo Hou, Xinhang Wei, Qi Wang

{"title":"A digital twin for tracking and forecasting glycemia with septic patients in ICUs.","authors":"Xiang Cao, Chao Cai, Jianguo Hou, Xinhang Wei, Qi Wang","doi":"10.1038/s44324-026-00132-2","DOIUrl":"https://doi.org/10.1038/s44324-026-00132-2","url":null,"abstract":"We present a digital twin framework for real-time glucose monitoring and forecasting in septic patients admitted to intensive care units (ICUs). The framework integrates advanced machine learning models trained on continuous glucose measurements with a dynamic digital twin workflow that enables rapid deployment to individual patients, ongoing model assessment, updating with newly acquired data, and personalized predictive decision support. Built on a foundation model-a pretrained time-series transformer-the digital twin adapts as new patient data become available and generates rolling near-term glucose forecasts in real time. To evaluate adaptability and computational efficiency, we deployed the pretrained model to ten septic patients and compared multiple personalization strategies, including zero-shot inference, linear probing, full fine-tuning, and staged fine-tuning. The results show that the model can be initialized and personalized for a new patient within seconds on a standard laptop while maintaining accurate glucose forecasts across varying data conditions. These findings demonstrate the feasibility of real-time digital twin personalization in resource-constrained, high-acuity clinical environments and highlight the potential of digital twins as scalable, AI-enabled platforms for continuous physiological monitoring, clinical decision support, and individualized treatment design in the ICU.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121751","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}

引用次数: 0

Liver androgen receptor knockout protects female mice from high fat diet-induced insulin resistance. 肝脏雄激素受体敲除保护雌性小鼠免受高脂肪饮食诱导的胰岛素抵抗。

npj Metabolic Health and Disease Pub Date : 2026-10-01 DOI: 10.1038/s44324-026-00133-1

Md Ahasanur Rahman, Demarrius Young, Taylor Southward, Taylor Lofton, Claire Falzarano, Ella Damaser, Andre Wilson, Damon Ross, Dwight Curry, Jacob Maynard, Jasmine Gray, Jason Lett, Rabia Qutab, Vaisakh Nair, Stanley Andrisse

{"title":"Liver androgen receptor knockout protects female mice from high fat diet-induced insulin resistance.","authors":"Md Ahasanur Rahman, Demarrius Young, Taylor Southward, Taylor Lofton, Claire Falzarano, Ella Damaser, Andre Wilson, Damon Ross, Dwight Curry, Jacob Maynard, Jasmine Gray, Jason Lett, Rabia Qutab, Vaisakh Nair, Stanley Andrisse","doi":"10.1038/s44324-026-00133-1","DOIUrl":"https://doi.org/10.1038/s44324-026-00133-1","url":null,"abstract":"High-fat diet (HFD) feeding induces reduced insulin-stimulated AKT phosphorylation with notable sex- and tissue-specific variability, yet the contribution of hepatic androgen receptor (AR) signaling to these effects remains unclear. To investigate the role of hepatic AR in metabolic regulation under dietary stress, liver-specific AR knockout (LivARKO) and wild-type (WT) mice of both sexes were fed control or HFD diets for up to 3 months. HFD impaired insulin-stimulated Akt phosphorylation across liver, skeletal muscle, and white adipose tissue in WT mice. In females, LivARKO preserved hepatic insulin sensitivity and attenuated HFD-induced induction of gluconeogenic genes Pck1 and G6pc, indicating protection from hepatic insulin resistance. This effect was not observed in skeletal muscle or adipose tissue. In contrast, male LivARKO mice showed no protection from HFD-induced insulin resistance and exhibited further upregulation of hepatic Pck1 and G6pc expression compared with WT males. These findings demonstrate a sexually dimorphic role for hepatic AR in regulating insulin signaling and glucose metabolism during HFD feeding. Targeting hepatic AR signaling may offer a sex-specific strategy for mitigating diet-induced metabolic dysfunction and improving metabolic health outcomes.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121870","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}

引用次数: 0

Childhood cancer and future cardiometabolic health. 儿童癌症和未来的心脏代谢健康

npj Metabolic Health and Disease Pub Date : 2026-09-29 DOI: 10.1038/s44324-026-00128-y

Abel Plaza-Florido, Pedro Carrera-Bastos, Shlomit Radom-Aizik, Inmaculada Pérez-Prieto, Francesca Lanfranconi, Gonzalo Saco-Ledo, Raquel Revuelta-Iniesta, Kirsten K Ness, Borja Del Pozo Cruz, Carmen Fiuza-Luces, Alejandro Lucia

引用次数: 0

Author Correction: An oral tyrosine challenge test for functional phenotyping of microbiota-derived phenyl sulfate production. 作者更正：口服酪氨酸激发试验用于微生物衍生的硫酸苯生产的功能表型。

npj Metabolic Health and Disease Pub Date : 2026-09-11 DOI: 10.1038/s44324-026-00134-0

Ting-Yun Lin, Szu-Chun Hung, Takaaki Abe

引用次数: 0

Diabetic plaque calcification: mechanisms, imaging phenotypes, and clinical implications. 糖尿病斑块钙化：机制、影像学表型和临床意义。

npj Metabolic Health and Disease Pub Date : 2026-09-02 DOI: 10.1038/s44324-026-00129-x

Mengmeng Zhu, Wenting Wang, Shihan Xu, Yiwen Li, Yanfei Liu, Yue Liu

引用次数: 0

Neurons run on fat. 神经元靠脂肪运转。

npj Metabolic Health and Disease Pub Date : 2026-09-02 DOI: 10.1038/s44324-026-00130-4

Rui Qi Teo, Gio Fidelito, Matthew J Watt, Garron T Dodd

引用次数: 0

Higher semaglutide dose is associated with lower neuropsychiatric event incidence independent of weight loss. 较高的西马鲁肽剂量与较低的神经精神事件发生率相关，与体重减轻无关。

npj Metabolic Health and Disease Pub Date : 2026-09-01 DOI: 10.1038/s44324-026-00131-3

Karthik Murugadoss, A J Venkatakrishnan, Venky Soundararajan

{"title":"Higher semaglutide dose is associated with lower neuropsychiatric event incidence independent of weight loss.","authors":"Karthik Murugadoss, A J Venkatakrishnan, Venky Soundararajan","doi":"10.1038/s44324-026-00131-3","DOIUrl":"10.1038/s44324-026-00131-3","url":null,"abstract":"GLP1 receptor agonists (GLP-1RAs) have transformed obesity treatment, but their impact on neuropsychiatric outcomes remains poorly understood. We conducted an observational study of 63,215 patients with preexisting neuropsychiatric conditions and evaluated 24 incident neuropsychiatric outcomes following treatment initiation. In propensity-matched analyses, semaglutide was associated with broadly lower neuropsychiatric event risk over two years compared with metformin, SGLT2 inhibitors, and DPP-4 inhibitors. Within the semaglutide-treated cohort, higher attained dose during the first two years after treatment initiation (\"pre-landmark period\") was associated with significantly lower incidence during the subsequent two years (\"post-landmark period\") of substance-related disorders (P < 0.001), mood disorders (P < 0.001), anxiety- and stress-related disorders (P < 0.001), central nervous system (CNS) atrophies (P < 0.001), neuromuscular disorders (P = 0.013), eating/sleep/behavioral disorders (P = 0.022), and personality/impulse-control disorders (P = 0.028). Consistent with prior clinical trials, the post-landmark incidence of dementia or CNS degenerative diseases was similar between the high-dose and low-dose semaglutide cohorts (P = 0.15). For most neuropsychiatric diagnoses, post-landmark incidence was strongly associated with the maximum attained dose. In contrast, incident cognitive symptoms and speech/language symptoms were more closely associated with weight loss (p < 0.001 and p < 0.003, respectively). Bulk and single-cell transcriptomic analyses identified low-level, regionally restricted GLP1R transcript signals in central and peripheral nervous system tissues, providing hypothesis-generating context for future experimental investigation. Together, these findings support an association between semaglutide exposure and multiple neuropsychiatric outcomes, and motivate prospective mechanistic and clinical studies.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13534496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877110","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}

引用次数: 0

Causal mediation pathways in continuous postprandial glucose monitoring for type 1 diabetes patients. 1型糖尿病患者餐后连续血糖监测的因果中介途径

npj Metabolic Health and Disease Pub Date : 2026-08-27 DOI: 10.1038/s44324-026-00127-z

Spencer Hilligoss, Annie Qu

{"title":"Causal mediation pathways in continuous postprandial glucose monitoring for type 1 diabetes patients.","authors":"Spencer Hilligoss, Annie Qu","doi":"10.1038/s44324-026-00127-z","DOIUrl":"10.1038/s44324-026-00127-z","url":null,"abstract":"Managing postprandial glucose in Type 1 Diabetes Mellitus (T1DM) requires understanding how carbohydrate intake affects glucose through both direct pathways and insulin-mediated compensation. Standard analyses treat insulin as a confounder rather than a mediator, obscuring these distinct causal channels and patient-level heterogeneity in carbohydrate response. Using meal-centered continuous glucose monitoring windows from twelve adults in the OhioT1DM cohorts, we apply causal mediation analysis to decompose the total effect of carbohydrate intake on glucose change into average direct (ADE), insulin-mediated (ACME), and total effects, by meal type and across outcome quantiles. To adjust for pre-meal confounding, we introduce a Causally-constrained Linear Autoencoder that learns low-dimensional representations improving adjustment for measured pre-meal state. Across cohorts, carbohydrate intake raises postprandial glucose chiefly through a large direct effect that insulin only partially offsets. The prespecified primary endpoint, the pooled ADE of a + 30 g contrast at two h, is large and highly significant, robust to multiple-testing correction, and replicates in the independent DiaTrend cohort (54 adults); the insulin-mediated effect is comparatively small. Meal- and quantile-specific signals, including greater dinner-time excursions, do not survive false-discovery-rate correction and are reported as hypothesis-generating. These results localize where postprandial insulin dosing may be refined.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841918","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}

引用次数: 0

Reappraising obesity management in the GLP-1 receptor agonist era. 重新评价GLP-1受体激动剂时代的肥胖管理。

npj Metabolic Health and Disease Pub Date : 2026-08-20 DOI: 10.1038/s44324-026-00126-0

T Christmas, A R Ahmed, T M-M Tan

引用次数: 0