npj Metabolic Health and Disease最新文献

{"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}

{"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}

{"title":"Chain splitting of insulin: an underlying mechanism of insulin resistance?","authors":"Christian N. Cramer, František Hubálek, Christian Lehn Brand, Hans Helleberg, Peter Kurtzhals, Jeppe Sturis","doi":"10.1038/s44324-024-00042-1","DOIUrl":"10.1038/s44324-024-00042-1","url":null,"abstract":"Despite decades of intense research, the mechanisms underlying insulin resistance are still poorly understood. What if one of the major causes of insulin resistance is not related to defects in the target tissues and/or insulin receptor signaling, but rather to a reduced survival of endogenously secreted insulin on its way to activating the receptor on the cell surface of the target tissues? Here, we present data and lay out arguments in support of this novel hypothesis, which is fundamentally different from the common view that insulin resistance is caused by the body’s cells becoming less sensitive to insulin.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00042-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862431","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}

{"title":"Too old for healthy aging? Exploring age limits of longevity treatments","authors":"Prerana Shrikant Chaudhari, Maria A. Ermolaeva","doi":"10.1038/s44324-024-00040-3","DOIUrl":"10.1038/s44324-024-00040-3","url":null,"abstract":"It is well documented that aging elicits metabolic failures, while poor metabolism contributes to accelerated aging. Metabolism in general, and energy metabolism in particular are also effective entry points for interventions that extend lifespan and improve organ function during aging. In this review, we discuss common metabolic remedies for healthy aging from the angle of their potential age-specificity. We demonstrate that some well-known metabolic treatments are mostly effective in young and middle-aged organisms, while others maintain high efficacy independently of age. The mechanistic basis of presence or lack of the age limitations is laid out and discussed.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00040-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821514","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}

{"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}

{"title":"Mitochondrial dysfunction in acute and post-acute phases of COVID-19 and risk of non-communicable diseases","authors":"Helena Borland Madsen, Jon Ambæk Durhuus, Ove Andersen, Per thor Straten, Anne Rahbech, Claus Desler","doi":"10.1038/s44324-024-00038-x","DOIUrl":"10.1038/s44324-024-00038-x","url":null,"abstract":"The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in widespread morbidity and mortality, with a significant portion of the affected population experiencing long-term health complications. This review explores the mechanisms of mitochondrial dysfunction in both the acute and post-acute phases of COVID-19, highlighting its impact on various organs and its potential role in the development of non-communicable diseases (NCDs). We discuss how SARS-CoV-2 directly affects mitochondrial function and the role of the virus-induced immune response in exacerbating mitochondrial impairment. This review highlights the critical role of mitochondria in COVID-19 pathogenesis and the importance of addressing mitochondrial health to mitigate acute and chronic effects of the disease.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00038-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762919","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}

{"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}

{"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}

{"title":"Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α","authors":"Nicola M. Sergienko, Adam J. Trewin, Helen Kiriazis, Antonia J. A. Raaijmakers, Daniel G. Donner, Victoria C. Garside, Kelly A. Smith, James R. Bell, Kimberley M. Mellor, Lea M. D. Delbridge, Julie R. McMullen, Kate L. Weeks","doi":"10.1038/s44324-024-00033-2","DOIUrl":"10.1038/s44324-024-00033-2","url":null,"abstract":"Protein phosphatase 2A (PP2A) regulatory subunit B55α has been implicated in the transcriptional regulation of cardiac growth and fibrosis by suppressing HDAC5/MEF2 signalling in cardiomyocytes. We created and characterised two mouse models with global or cardiomyocyte-specific disruption of the gene encoding B55α (Ppp2r2a) to conduct the first detailed exploration of B55α in the heart. Global homozygous B55α knockout mice died in utero, while heterozygous mice had thinner left ventricular walls at 12 months, an effect more pronounced in males. At 10–12 weeks of age, cardiomyocyte-specific B55α knockout mice displayed normal cardiac morphology with increased left ventricular collagen deposition, identifying B55α as a negative regulator of cardiac fibrosis. Gene expression analyses demonstrated extensive remodelling of the cardiac transcriptome in male but not female mice, revealing a sexually dimorphic role for B55α in cardiac transcriptional regulation. These findings provide a basis for future work investigating B55α in cardiac stress settings.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00033-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595719","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}

{"title":"Incretin-based therapies for the treatment of obesity-related diseases","authors":"Irene Caruso, Angelo Cignarelli, Gian Pio Sorice, Sebastio Perrini, Francesco Giorgino","doi":"10.1038/s44324-024-00030-5","DOIUrl":"10.1038/s44324-024-00030-5","url":null,"abstract":"Obesity-related disability-adjusted life years (DALYs) are expected to increase by approximately 40% from 2020 to 2030. DALYs and mortality related to obesity are the consequence of multiple comorbidities such as cardiovascular (i.e., heart failure) and metabolic diseases (i.e. type 2 diabetes [T2D], metabolic dysfunction-associated steatotic liver disease [MASLD]). Lifestyle interventions represent the foundation of obesity treatment, yet an escalation to pharmacological and/or surgical interventions is often needed. Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development. Incretin-based therapies have been associated with a body weight (BW) reduction of ≥5% in at least half of patients in most randomized controlled trials (RCT) and real-world studies (RWS). Semaglutide and tirzepatide have also displayed a mean 60–69% 10-years relative risk reduction of T2D development. In line with evidence accrued in patients with T2D, incretin-based therapies produced a favorable effect on traditional cardiovascular risk factors, such as lipids and blood pressure, and even reduced the risk of major cardiovascular events and heart failure-related events in individuals with obesity, as recently demonstrated for the first time in the SELECT trial with semaglutide 2.4 mg once-weekly. Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD. Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the underlying mechanism, whether involving direct effects on target tissues or mediated by improvement in BW, glucose levels and other CV risk factors.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00030-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595724","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}