npj Metabolic Health and Disease最新文献

Adolescence as a key developmental window for nutrition promotion and cardiometabolic disease prevention. 青春期是促进营养和预防心脏代谢疾病的关键发育窗口。

npj Metabolic Health and Disease Pub Date : 2025-10-10 DOI: 10.1038/s44324-025-00082-1

Bianca Carducci, Zheng Hao Chen, Susan C Campisi, Kozeta Miliku

引用次数: 0

Sterile inflammation in MASH: emerging role of extracellular RNA and therapeutic strategies. 无菌炎症在MASH：细胞外RNA的新作用和治疗策略。

npj Metabolic Health and Disease Pub Date : 2025-10-06 DOI: 10.1038/s44324-025-00083-0

Sana Raza, Rukshana Mahamood, Pratik Medhe, Ambuj Shahi, Abhishek Yadav, Archana Tewari, Rohit A Sinha

{"title":"Sterile inflammation in MASH: emerging role of extracellular RNA and therapeutic strategies.","authors":"Sana Raza, Rukshana Mahamood, Pratik Medhe, Ambuj Shahi, Abhishek Yadav, Archana Tewari, Rohit A Sinha","doi":"10.1038/s44324-025-00083-0","DOIUrl":"10.1038/s44324-025-00083-0","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced form, metabolic dysfunction-associated steatohepatitis (MASH), are major global health issues involving metabolic dysfunction, hepatic lipotoxicity, and chronic inflammation. A key driver of MASH pathogenesis is sterile inflammation, a non-infectious immune response triggered by molecules that are released from injured or dying liver cells. These molecules termed as damage-associated molecular patterns (DAMPs), which activate innate immune receptors, such as Toll-like receptors (TLRs), NOD-like receptors, and the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway to encourage inflammatory signaling, cytokine production, immune cell recruitment, and ultimately fibrogenic activation in MASH. Sterile inflammation sits at the crossroads of metabolic injury and immune activation in MASH and drives disease progression from simple fat build-up to irreversible liver damage. Targeting these sterile inflammatory pathways appears to be an attractive approach for halting or reversing hepatic inflammation and fibrogenic activation in MASH. Extracellular RNAs (eRNAs) have recently been identified as potent DAMPs that trigger sterile inflammation in MASH by engaging in TLR3 signaling. Furthermore, RNase1-based treatments have been proposed as novel therapeutic strategies to interrupt the self-sustaining loop of inflammatory signaling induced by eRNA in MASH. In this review, we discuss the key molecular mechanisms that fuel sterile inflammation in MASLD/MASH, highlighting eRNA as novel therapeutic targets to restrict inflammation in MASH.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"39"},"PeriodicalIF":0.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240694","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

Author Correction: Fasting mimicking diet cycles versus a Mediterranean diet and cardiometabolic risk in overweight and obese hypertensive subjects: a randomized clinical trial. 作者更正：在超重和肥胖高血压受试者中，模拟饮食周期的禁食与地中海饮食和心脏代谢风险：一项随机临床试验。

npj Metabolic Health and Disease Pub Date : 2025-09-23 DOI: 10.1038/s44324-025-00084-z

Amrendra Mishra, Maura Fanti, Xinzhou Ge, Don Vaughn, Sebastian Brandhorst, Min Wei, Kurt M Hong, Matteo Pellegrini, Hanno Pijl, Mark C Houston, Valter D Longo

引用次数: 0

Mitochondrial uncoupling, energy substrate utilization, and brown adipose tissue as therapeutic targets in cancer. 线粒体解偶联、能量底物利用和棕色脂肪组织作为癌症的治疗靶点。

npj Metabolic Health and Disease Pub Date : 2025-09-22 DOI: 10.1038/s44324-025-00080-3

Maurizio Ragni, Chiara Ruocco, Enzo Nisoli

{"title":"Mitochondrial uncoupling, energy substrate utilization, and brown adipose tissue as therapeutic targets in cancer.","authors":"Maurizio Ragni, Chiara Ruocco, Enzo Nisoli","doi":"10.1038/s44324-025-00080-3","DOIUrl":"10.1038/s44324-025-00080-3","url":null,"abstract":"Mitochondria play a central role in regulating cellular energy metabolism, redox homeostasis, and biosynthesis. Mitochondrial uncoupling, through the alteration in the permeability of the inner mitochondrial membrane (IMM) to the leak of protons without adenosine triphosphate (ATP) synthesis, regulates thermogenesis, glucose and lipid metabolism, and reactive oxygen species (ROS) generation. In brown adipose tissue (BAT), proton leak via uncoupling protein 1 (UCP1) is essential for thermogenesis and has been shown to improve systemic glucose homeostasis, and recent studies indicate that BAT activation can also suppress tumor growth by competing with cancer cells for glucose. Several small-molecule mitochondrial uncouplers have demonstrated anticancer effects in preclinical models, although endogenous UCPs-particularly UCP2-are often upregulated in tumors, where they may support tumor growth by buffering ROS and increasing metabolic flexibility. These seemingly contradictory observations highlight the context-dependent effects of mitochondrial uncoupling in cancer. Here, we review current understanding of mitochondrial uncoupling mechanisms, the roles of UCP isoforms, and the metabolic interplay between BAT, cancer cells, and the tumor microenvironment, with a focus on therapeutic implications.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"37"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126727","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

GLP-1 receptor agonism results in reduction in hepatic ethanol metabolism. GLP-1受体激动作用导致肝脏乙醇代谢减少。

npj Metabolic Health and Disease Pub Date : 2025-09-18 DOI: 10.1038/s44324-025-00077-y

Frhaan Zahrawi, Arumugam Suyavaran, Bubu A Banini, Wajahat Z Mehal

引用次数: 0

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS. 先天免疫增强可能引发慢性炎症、疲劳和运动后不适。

npj Metabolic Health and Disease Pub Date : 2025-09-03 DOI: 10.1038/s44324-025-00079-w

Xiaoyu Che, Amit Ranjan, Cheng Guo, Keming Zhang, Rochelle Goldsmith, Susan Levine, Kegan J Moneghetti, Yali Zhai, Liner Ge, Nischay Mishra, Mady Hornig, Lucinda Bateman, Nancy G Klimas, Jose G Montoya, Daniel L Peterson, Sabra L Klein, Oliver Fiehn, Anthony L Komaroff, W Ian Lipkin

{"title":"Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.","authors":"Xiaoyu Che, Amit Ranjan, Cheng Guo, Keming Zhang, Rochelle Goldsmith, Susan Levine, Kegan J Moneghetti, Yali Zhai, Liner Ge, Nischay Mishra, Mady Hornig, Lucinda Bateman, Nancy G Klimas, Jose G Montoya, Daniel L Peterson, Sabra L Klein, Oliver Fiehn, Anthony L Komaroff, W Ian Lipkin","doi":"10.1038/s44324-025-00079-w","DOIUrl":"10.1038/s44324-025-00079-w","url":null,"abstract":"Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained fatigue, post-exertional malaise (PEM), and cognitive dysfunction. ME/CFS patients often report a prodrome consistent with infection. We present a multi-omics analysis based on plasma metabolomic and proteomic profiling, and immune responses to microbial stimulation, before and after exercise. We report evidence of an exaggerated innate immune response after exposure to microbial antigens; impaired energy production involving the citric acid cycle, beta-oxidation of fatty acids, and urea cycle energy production from amino acids; systemic inflammation linked to lipid abnormalities; disrupted extracellular matrix homeostasis with release of endogenous ligands that promote inflammation; reduced cell-cell adhesion and associated gut dysbiosis; complement activation; redox imbalance reflected by disturbances in copper-dependent antioxidant pathways; and dysregulation of tryptophan-serotonin-kynurenine pathways. Many abnormalities were worse following exercise and correlated with the intensity of symptoms. Our findings may inform development of targeted therapeutic interventions for ME/CFS and PEM.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"34"},"PeriodicalIF":0.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995021","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

Metabolomic-based aging clocks. 基于代谢组学的衰老时钟。

npj Metabolic Health and Disease Pub Date : 2025-09-03 DOI: 10.1038/s44324-025-00078-x

A Ibáñez de Opakua, R Conde, A de Diego, M Bizkarguenaga, N Embade, S C Lu, J M Mato, O Millet

引用次数: 0

Cave adaptation favors aging resilience in the Mexican tetra. 洞穴适应有利于墨西哥四环树的衰老恢复能力。

npj Metabolic Health and Disease Pub Date : 2025-08-01 DOI: 10.1038/s44324-025-00069-y

Ansa E Cobham, Alexander Kenzior, Pedro Morales-Sosa, Jose Emmanuel Javier, Selene Swanson, Christopher Wood, Nicolas Rohner

{"title":"Cave adaptation favors aging resilience in the Mexican tetra.","authors":"Ansa E Cobham, Alexander Kenzior, Pedro Morales-Sosa, Jose Emmanuel Javier, Selene Swanson, Christopher Wood, Nicolas Rohner","doi":"10.1038/s44324-025-00069-y","DOIUrl":"10.1038/s44324-025-00069-y","url":null,"abstract":"All animals age, but the rate of aging across species varies widely. The environmental pressures and molecular factors underlying this remarkable diversity in aging across species remains largely enigmatic. The Mexican tetra, Astyanax mexicanus, provides an intriguing new model to study how adaptation to different environments alter aging. This species exists as the river-dwelling surface fish, living in food and light rich environments, and the blind cave-adapted cavefish, thriving in dark, nutrient-limited, caves. How adaption to these extreme environments alter aging in this species remains unknown. Here, we compared aging markers between surface and cavefish populations, focusing on morphological, behavioral changes, and molecular signatures. We found aging markers were more pronounced in surface fish, but less distinct in aged cavefish. We also observed that insulin receptor mutation is limited in its impact to increase lifespan in cavefish. Instead, metabolic shifts, particularly in mitochondrial function, may contribute to cavefish's extended longevity.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"33"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765973","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

The metabolic advantage of being young and male in obesity treatment outcomes in mice. 年轻和雄性在小鼠肥胖治疗结果中的代谢优势。

npj Metabolic Health and Disease Pub Date : 2025-08-01 DOI: 10.1038/s44324-025-00065-2

Amanda S Dirnberger, Elen Yanina Aguirre-Rodriguez, Elias Carlos Aguirre-Rodriguez, John O Degraft Hanson, Yanping Sun, Dave Delima, Benjamin F Bykov, Aneirson Francisco da Silva, Marko Kraljević, Fernando Augusto Silva Marins, Ana Bf Emiliano

{"title":"The metabolic advantage of being young and male in obesity treatment outcomes in mice.","authors":"Amanda S Dirnberger, Elen Yanina Aguirre-Rodriguez, Elias Carlos Aguirre-Rodriguez, John O Degraft Hanson, Yanping Sun, Dave Delima, Benjamin F Bykov, Aneirson Francisco da Silva, Marko Kraljević, Fernando Augusto Silva Marins, Ana Bf Emiliano","doi":"10.1038/s44324-025-00065-2","DOIUrl":"10.1038/s44324-025-00065-2","url":null,"abstract":"Although diversity in clinical trials is important to test the efficacy of a treatment, weight loss trials rarely account for age and sex. To highlight this deficiency, we set out to test whether age and sex affect WAT mobilization after weight loss surgery or intermittent fasting, in an obese mouse model. Here we show that male sex, youth, and WAT transcriptomic plasticity are characteristics associated with improved weight loss outcomes. Conversely, aging impairs WAT mobilization and transcriptomic plasticity. Greater surgical weight loss is associated with changes in the expression of genes relevant to the IL17 inflammatory signaling pathway, angiotensin converting enzyme 2 (ACE2) signaling, lipolysis, carbohydrate metabolism and adipocyte differentiation. In conclusion, female sex and older age appear to hinder molecular processes necessary for the reversal of WAT expansion. Future studies should examine the relevance of these findings to human obesity therapeutics.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"32"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765974","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

Skeletal muscle proteomics: considerations and opportunities. 骨骼肌蛋白质组学：考虑和机会。

npj Metabolic Health and Disease Pub Date : 2025-07-02 DOI: 10.1038/s44324-025-00073-2

Julian P H Wong, Yaan-Kit Ng, Jeppe Kjærgaard, Ronnie Blazev, Atul S Deshmukh, Benjamin L Parker

引用次数: 0