npj Metabolic Health and Disease最新文献

Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.

npj Metabolic Health and Disease Pub Date : 2025-01-01 Epub Date: 2025-02-03 DOI: 10.1038/s44324-025-00049-2

Fivos Borbolis, Christina Ploumi, Konstantinos Palikaras

{"title":"Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases.","authors":"Fivos Borbolis, Christina Ploumi, Konstantinos Palikaras","doi":"10.1038/s44324-025-00049-2","DOIUrl":"10.1038/s44324-025-00049-2","url":null,"abstract":"Calcium signaling plays a pivotal role in diverse cellular processes through precise spatiotemporal regulation and interaction with effector proteins across distinct subcellular compartments. Mitochondria, in particular, act as central hubs for calcium buffering, orchestrating energy production, redox balance and apoptotic signaling, among others. While controlled mitochondrial calcium uptake supports ATP synthesis and metabolic regulation, excessive accumulation can trigger oxidative stress, mitochondrial membrane permeabilization, and cell death. Emerging findings underscore the intricate interplay between calcium homeostasis and mitophagy, a selective type of autophagy for mitochondria elimination. Although the literature is still emerging, this review delves into the bidirectional relationship between calcium signaling and mitophagy pathways, providing compelling mechanistic insights. Furthermore, we discuss how disruptions in calcium homeostasis impair mitophagy, contributing to mitochondrial dysfunction and the pathogenesis of common neurodegenerative diseases.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257769","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

Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice.

npj Metabolic Health and Disease Pub Date : 2025-01-01 Epub Date: 2025-02-03 DOI: 10.1038/s44324-024-00039-w

Eleni Beli, Yuanqing Yan, Leni Moldovan, Todd A Lydic, Preethi Krishman, Sarah A Tersey, Yaqian Duan, Tatiana E Salazar, James M Dominguez, Dung V Nguyen, Abigail Cox, Sergio Li Calzi, Craig Beam, Raghavendra G Mirmira, Carmella Evans-Molina, Julia V Busik, Maria B Grant

{"title":"Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice.","authors":"Eleni Beli, Yuanqing Yan, Leni Moldovan, Todd A Lydic, Preethi Krishman, Sarah A Tersey, Yaqian Duan, Tatiana E Salazar, James M Dominguez, Dung V Nguyen, Abigail Cox, Sergio Li Calzi, Craig Beam, Raghavendra G Mirmira, Carmella Evans-Molina, Julia V Busik, Maria B Grant","doi":"10.1038/s44324-024-00039-w","DOIUrl":"10.1038/s44324-024-00039-w","url":null,"abstract":"Strategies to improve metabolic health include calorie restriction, time restricted eating and fasting several days per week or month. These approaches have demonstrated benefits for individuals experiencing obesity, metabolic syndrome, and prediabetes. However, their impact on established diabetes remains incompletely studied. The chronicity of type 2 diabetes (T2D) requires that interventions must be undertaken for extended periods of time, typically the entire lifetime of the individual. In this study, we examined the impact of intermittent fasting (IF), with an every-other-day protocol for a duration of 6 months in a murine model of T2D, the db/db (D) mouse on metabolism and liver steatosis. We compared D-IF mice with diabetic ad-libitum (AL; D-AL), control-IF (C-IF) and control-AL (C-AL) cohorts. We demonstrated using lipidomic, microbiome, metabolomic and liver transcriptomic studies that chronic IF improved carbohydrate utilization and glucose homeostasis without weight loss and reduced white adipose tissue inflammation and significantly impacted lipid metabolism in the liver. Microbiome studies and predicted functional analysis of gut microbiota showed that IF increased beneficial bacteria involved in sphingolipid (SL) metabolism. The metabolomic studies showed that oxidation of lipid species and ceramide levels were reduced in D-IF compared to D-AL. The liver lipidomic analysis and liver microarray confirmed a reduction in overall lipid content in D-IF mice compared to D-AL mice, especially in the feeding state as well as an overall reduction in oxidized lipids and ceramides. These studies support that long-term IF can improve glucose homeostasis and dramatically altered lipid metabolism in the absence of weight loss.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":"3 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257770","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

Intermittent fasting as a treatment for obesity in young people: a scoping review 间歇性禁食作为治疗年轻人肥胖的一种方法：范围综述

npj Metabolic Health and Disease Pub Date : 2024-12-30 DOI: 10.1038/s44324-024-00041-2

Jomanah Bakhsh, Sarah-Jeanne Salvy, Alaina P. Vidmar

{"title":"Intermittent fasting as a treatment for obesity in young people: a scoping review","authors":"Jomanah Bakhsh, Sarah-Jeanne Salvy, Alaina P. Vidmar","doi":"10.1038/s44324-024-00041-2","DOIUrl":"10.1038/s44324-024-00041-2","url":null,"abstract":"Intermittent fasting focuses on the timing of eating rather than diet quality or energy intake, with evidence supporting its effects on weight loss and improvements in cardiometabolic outcomes in adults with obesity. However, there is limited evidence for its feasibility and efficacy in young people. To address this, a scoping review was conducted to examine intermittent fasting regimens in individuals aged 10 to 25 for the treatment of obesity focusing on methodology, intervention parameters, outcomes, adherence, feasibility, and efficacy. Due to the paucity of evidence in this age group, to adequately assess feasibility and adherence, all published studies of intermittent fasting in this age category, regardless of weight status and treatment intention, were included in the review. The review included 34 studies (28 interventional studies and 6 observational studies) with 893 participants aged 12 to 25. Interventions varied with 9 studies in cohorts with obesity utilizing intermittent fasting as an obesity treatment. Thirteen studies utilized 8-h time-restricted eating. Primary outcomes included cardiometabolic risk factors (7/28), anthropometric measurements (7/28), body composition (5/28), muscular performance (4/28), feasibility (1/28), and others (4/28). All 9 studies conducted in young people with obesity reported some degree of weight loss, although the comparator groups varied significantly. This review underscores the various utilizations of intermittent fasting in this age group and highlights its potential in treating obesity. However, the findings emphasize the need for rigorous studies with standardized frameworks for feasibility to ensure comparability and determine intermittent fasting’s practicality in this age group depending on the treatment outcome of interest.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00041-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906112","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 effect of high-sugar feeding on rodent metabolic phenotype: a systematic review and meta-analysis 高糖摄食对啮齿动物代谢表型的影响：系统回顾和荟萃分析

npj Metabolic Health and Disease Pub Date : 2024-12-30 DOI: 10.1038/s44324-024-00043-0

Sophie Lucic Fisher, G. Jean Campbell, Alistair Senior, Kim Bell-Anderson

{"title":"The effect of high-sugar feeding on rodent metabolic phenotype: a systematic review and meta-analysis","authors":"Sophie Lucic Fisher, G. Jean Campbell, Alistair Senior, Kim Bell-Anderson","doi":"10.1038/s44324-024-00043-0","DOIUrl":"10.1038/s44324-024-00043-0","url":null,"abstract":"Dietary sugar consumption has been linked to increased cardiometabolic disease risk, although it is unclear if this is independent of increases in body weight and adiposity. Additionally, many preclinical animal studies provide liquid sugar which more readily leads to excess consumption and weight gain, confounding any outcomes driven by high-sugar intake alone. To gain clarity on this, we conducted a systematic review and meta-analysis exclusively investigating the effect of isocaloric high-sugar, low-fat solid diet formulations containing fructose or sucrose, on cardiometabolic health in rodents. Overall, we found strong evidence that fructose and sucrose have effects on metabolic health, independent of body weight gain. High-sugar feeding, with fructose in particular, altered liver phenotype; ALT (d = 1.08; 0.66, 1.5), triglyceride content (d = 0.52; 0.25, 0.78), cholesterol (d = 0.59; 0.16, 1.03) and liver mass (d = 0.93; 0.37, 1.48), and glucose tolerance; fasting glucose (d = 0.60; 0.18, 1.01) and fasting insulin (d = 0.42; 0.07, 0.77) but not body weight or energy intake. Our review also highlights the lack of data reported on adiposity and in female rodents. This is the first meta-analysis to synthesise all current rodent solid diet high-sugar studies, while adjusting them for confounders (fat content, time spent on diet and age started on diet) and suggests that high-sugar dietary intake and composition alters metabolic health of mice regardless of weight gain.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00043-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906125","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

Chain splitting of insulin: an underlying mechanism of insulin resistance? 胰岛素链分裂：胰岛素抵抗的潜在机制？

npj Metabolic Health and Disease Pub Date : 2024-12-18 DOI: 10.1038/s44324-024-00042-1

Christian N. Cramer, František Hubálek, Christian Lehn Brand, Hans Helleberg, Peter Kurtzhals, Jeppe Sturis

引用次数: 0

Too old for healthy aging? Exploring age limits of longevity treatments 健康老龄化太老？探索长寿疗法的年龄限制

npj Metabolic Health and Disease Pub Date : 2024-12-12 DOI: 10.1038/s44324-024-00040-3

Prerana Shrikant Chaudhari, Maria A. Ermolaeva

引用次数: 0

SMRT-depleted conventional DCs maintain inflammation despite lower glycolysis via mTOR signalling and succinate oxidation 尽管通过mTOR信号传导和琥珀酸氧化降低糖酵解，但smrt缺失的传统dc仍维持炎症

npj Metabolic Health and Disease Pub Date : 2024-12-04 DOI: 10.1038/s44324-024-00034-1

Kaushik Sen, Rashmirekha Pati, Gyan Prakash Mishra, Subhasish Prusty, Sourya Prakash Nayak, Archana Tripathy, Shweta Chaudhary, Atimukta Jha, Arunita Patra, Priti Meena, Shaktiprasad Mishra, Ranjan Kumar Nanda, Alok Kumar Mantri, Bhawna Gupta, Sunil K. Raghav

{"title":"SMRT-depleted conventional DCs maintain inflammation despite lower glycolysis via mTOR signalling and succinate oxidation","authors":"Kaushik Sen, Rashmirekha Pati, Gyan Prakash Mishra, Subhasish Prusty, Sourya Prakash Nayak, Archana Tripathy, Shweta Chaudhary, Atimukta Jha, Arunita Patra, Priti Meena, Shaktiprasad Mishra, Ranjan Kumar Nanda, Alok Kumar Mantri, Bhawna Gupta, Sunil K. Raghav","doi":"10.1038/s44324-024-00034-1","DOIUrl":"10.1038/s44324-024-00034-1","url":null,"abstract":"Inflammatory diseases implicate a synchronised immune-metabolic rewiring to maintain homeostasis. The regulatory mechanisms governing the transcriptional control of immune-centric metabolic adjustments in dendritic cells (DCs) remains elusive. Recently we reported that Ncor2 (SMRT) loss of function in DCs potentiates strong inflammation. We found that SMRT depletion in DCs triggers a metabolic shift resulting in sustained and strong inflammation despite reduced glycolysis. This is in contrast to the widely accepted notion that glycolytic pathway activation is essential for inducing inflammation. Downregulation of mTOR emerged as a pivotal factor in attenuating the glycolytic rate. Significant metabolic alterations led to rewiring of the TCA-cycle by triggering anaplerotic glutamine catabolism and promoting succinate oxidation, thereby sustaining the inflammatory potential. Simultaneous treatment with succinate transport inhibitor DEBM and mTOR inducer Mhy1485 remarkably suppressed inflammation ex vivo and in vivo. Our findings also depicted an inverse correlation between SMRT levels with human autoimmune diseases.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00034-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762981","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

Mitochondrial dysfunction in acute and post-acute phases of COVID-19 and risk of non-communicable diseases COVID-19急性期和急性后期线粒体功能障碍与非传染性疾病风险

npj Metabolic Health and Disease Pub Date : 2024-12-04 DOI: 10.1038/s44324-024-00038-x

Helena Borland Madsen, Jon Ambæk Durhuus, Ove Andersen, Per thor Straten, Anne Rahbech, Claus Desler

引用次数: 0

Human adipose depots’ diverse functions and dysregulations during cardiometabolic disease 人类脂肪库在心脏代谢疾病中的多种功能和失调

npj Metabolic Health and Disease Pub Date : 2024-11-29 DOI: 10.1038/s44324-024-00036-z

Andreas Kraag Ziegler, Camilla Scheele

{"title":"Human adipose depots’ diverse functions and dysregulations during cardiometabolic disease","authors":"Andreas Kraag Ziegler, Camilla Scheele","doi":"10.1038/s44324-024-00036-z","DOIUrl":"10.1038/s44324-024-00036-z","url":null,"abstract":"Adipose tissue depots develop specific functions in a location dependent manner. In humans, this for example includes thermogenic capacity in the brown adipose supraclavicular, deep neck and perirenal depots, healthy lipid storage primarily in the gluteofemoral subcutaneous depot, and immunogenic support in the visceral omental depot. These distinct functions are at some point programmed into adipose progenitor cells, which retain some of the phenotype from the depot they originated from upon isolation and differentiation in vitro. Cardiometabolic diseases associate with body fat distribution, with an accumulation of lipids in the visceral depot accompanied by low grade inflammation and insulin resistance as a typical phenotype. However, well-functioning subcutaneous adipose tissue and brown adipose tissue contribute to a metabolically healthy phenotype, and it is therefore worth understanding the function and regulation of these adipocytes. In this review, we will discuss the dysregulations in distinct human adipose tissue depots associated with cardiometabolic disease, some of the consequences this has on whole body metabolism, and how depot-specific dysregulations might affect other adipose depots to progress a cardiometabolic disease condition.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00036-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754210","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

Variable bioenergetic sensitivity of neurons and astrocytes to insulin and extracellular glucose 神经元和星形胶质细胞对胰岛素和细胞外葡萄糖的生物能敏感性各不相同

npj Metabolic Health and Disease Pub Date : 2024-11-08 DOI: 10.1038/s44324-024-00037-y

Sophiya L. Sims, Hilaree N. Frazier, Sami L. Case, Ruei-Lung Lin, James N. Trosper, Hemendra J. Vekaria, Patrick G. Sullivan, Olivier Thibault

{"title":"Variable bioenergetic sensitivity of neurons and astrocytes to insulin and extracellular glucose","authors":"Sophiya L. Sims, Hilaree N. Frazier, Sami L. Case, Ruei-Lung Lin, James N. Trosper, Hemendra J. Vekaria, Patrick G. Sullivan, Olivier Thibault","doi":"10.1038/s44324-024-00037-y","DOIUrl":"10.1038/s44324-024-00037-y","url":null,"abstract":"Energy flow within cellular elements of the brain is a well-orchestrated, tightly regulated process, however, details underlying these functions at the single-cell level are still poorly understood. Studying hypometabolism in aging and neurodegenerative diseases may benefit from experimentation on unicellular bioenergetics. Here, we examined energy status in neurons and astrocytes using mixed hippocampal cultures and PercevalHR, an ATP:ADP nanosensor. We assessed exposures of several compounds including KCl, glutamate, FCCP, insulin, and glucose. A mitochondrial stress test was performed, and PercevalHR’s fluorescence was corrected for pH using pHrodo. Results demonstrate that PercevalHR can reliably report on the energetic status of two cell types that communicate in a mixed-culture setting. While KCl, glutamate, and FCCP showed clear changes in PercevalHR fluorescence, insulin and glucose responses were found to be more subtle and sensitive to extracellular glucose. These results may highlight mechanisms that mediate insulin sensitivity in the brain.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00037-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595705","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