Nature Reviews Endocrinology最新文献

{"title":"Glycogen metabolism: not just a one-trick pony","authors":"Dipsikha Biswas","doi":"10.1038/s41574-025-01152-6","DOIUrl":"https://doi.org/10.1038/s41574-025-01152-6","url":null,"abstract":"<p>Prior to the 1940s, glycogen was thought to be stored primarily in the liver and muscles and used during periods of high energy demand and/or low blood glucose availability. In 1942, Tuerkischer and Wertheimer showed that adipose tissue can also produce and store small amounts of glycogen, concurrent with periods of active lipid synthesis. J. M. Friedman and colleagues showed in 2008 that lipid synthesis in adipose tissues occurs via a glycogen intermediate, underlining the importance of glycogen turnover in the regulation of adipocyte energy metabolism. A 2021 <i>Nature</i> paper further extended the role of glycogen metabolism to include thermogenesis in adipocytes.</p><p>The low glycogen content in adipocytes was thought to be due to biophysical constraints imposed by the limited cytoplasmic space in these cells, but Tuerkischer and Wertheimer (in 1942) and other researchers later confirmed that glycogen turnover in adipose tissue changes with nutritional status. Glycogen content transiently increases with refeeding after fasting in both brown adipose tissue (BAT) and white adipose tissue (WAT) as well as following cold exposure in BAT, partly due to increased AKT phosphorylation and inactivation of GSK3, resulting in increased glycogen synthesis. Indeed, glycogen metabolism is crucial for BAT development, and abrogating glycogen turnover, either by knocking out (KO) <i>GYS1</i> (encoding glycogen synthase 1) or blocking glycophagy, prevents lipid droplet formation selectively in BAT.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"3 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA-based enzyme replacement for propionic acidaemia","authors":"Chuang Liu","doi":"10.1038/s41574-025-01150-8","DOIUrl":"https://doi.org/10.1038/s41574-025-01150-8","url":null,"abstract":"<p>Propionic acidaemia is an autosomal recessive metabolic disorder, typically presenting in neonates with vomiting, dehydration, feeding issues and rapid physical decline. Without prompt early intervention, symptoms can progress to seizures, coma and even death. Long-term complications include growth failure, neurological damage, heart and immune dysfunction, and pancreatitis. Propionic acidaemia is caused by pathogenic variants in two genes, <i>PCCA</i> or <i>PCCB</i>, which encode the α and β subunits of propionyl-coenzyme A (CoA) carboxylase (PCC), respectively. PCC, a mitochondrial enzyme consisting of six subunits each of PCCA and PCCB, converts propionyl-CoA to methylmalonyl-CoA. PCC deficiency leads to the toxic accumulation of propionyl-CoA and organic acids, resulting in an intoxication-type metabolic crisis. Aside from liver transplantation, management of propionic acidaemia focuses on survival and then quality of life; no therapies specifically target the underlying enzymatic defect through metabolic correction. A paper published in <i>Nature Communications</i> in 2020 reported the development of a messenger RNA (mRNA) therapy that achieved sustained metabolic correction in a mouse model of propionic acidaemia.</p><p>The researchers’ goal was straightforward: to produce functional PCC enzyme in vivo, thereby restoring liver metabolic function in patients with either PCCA or PCCB deficiency. To achieve this aim, the researchers devised lipid nanoparticles loaded with mRNAs encoding both human <i>PCCA</i> and <i>PCCB</i>. In cultured human fibroblasts treated with dual mRNA-loaded lipid nanoparticles, PCC expression was localized to mitochondria, and further optimization of the PCCA to PCCB mRNA molar ratio revealed that a 1:1 ratio yielded the highest PCC enzymatic activity in these cells. After a single intravenous dose of dual mRNA-loaded lipid nanoparticles into a hypomorphic mouse model of propionic acidaemia, levels of PCCA and PCCB in the liver were similar to typical levels in human liver. Given the need for repeat dosing to maintain PCC expression, the researchers conducted two long-term studies in propionic acidaemia hypomorphic mice: 0.5 or 2 mg/kg intravenous mRNA dosing every 3 weeks over 3 months, or 0.5 or 1 mg/kg monthly intravenous mRNA dosing over 6 months. Both studies showed dose-dependent increases in hepatic PCC activity and reductions in primary biomarkers in plasma (such as 2-methylcitrate, 3-hydroxypropionate and propionylcarnitine to acetylcarnitine ratio), with no observed adverse effects, indicating favourable tolerability. However, the study has some limitations: it did not assess whether treated mice developed antibodies against human PCC, and many symptoms of propionic acidaemia in patients are not present in propionic acidaemia hypomorphic mice, both of which could potentially limit clinical translation of these findings.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"21 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pituitary incidentaloma: a Pituitary Society international consensus guideline statement","authors":"Maria Fleseriu, Mark Gurnell, Ann McCormack, Hidenori Fukuoka, Andrea Glezer, Fabienne Langlois, Theodore H. Schwartz, Yona Greenman, Nidhi Agrawal, Amit Akirov, Irina Bancos, Cristina Capatina, Frederic Castinetti, Michael Catalino, Mirjam Christ-Crain, Liza Das, Andjela Drincic, Pamela U. Freda, Monica R. Gadelha, Andrea Giustina, Felicia Hanzu, Ken K. Y. Ho, Kristina Isand, Susana Mallea-Gil, Adam N. Mamelak, Hani J. Marcus, Meliha Melin Uygur, Mark Molitch, Lisa B. Nachtigall, Elisabeth Nowak, Alberto M. Pereira, Maria M. Pineyro, Ismat Shafiq, Luis Syro, Yutaka Takahashi, Elena V. Varlamov, Greisa Vila, Gabriel Zada, Niki Karavitaki, Shlomo Melmed","doi":"10.1038/s41574-025-01134-8","DOIUrl":"https://doi.org/10.1038/s41574-025-01134-8","url":null,"abstract":"<p>This Pituitary Society Consensus article presents an evidence-based consensus on the management of pituitary incidentaloma, defined as an unexpected sellar or parasellar finding incidentally discovered on an imaging study that was not performed for a clinically suspected pituitary lesion. Recommendations are offered for when endocrinology, neurosurgery and ophthalmology consultation, dedicated pituitary imaging, pituitary hormone testing and visual assessment are warranted for macroadenomas, microadenomas, cystic lesions and empty sella, as well as when surgical resection is indicated for incidental pituitary adenomas and cystic sellar lesions. Special considerations in patients with multiple endocrine neoplasia type 1, children and adolescents, older people, and pregnant women are addressed. The Consensus workshop concluded that diagnostic and management approaches should be individualized to the specific clinical context of an incidentally discovered pituitary lesion. Consultation with a multidisciplinary pituitary tumour centre of excellence should be considered in the presence of new or deteriorating lesion-specific signs or symptoms, particularly when surgical or other adjuvant interventions are being considered and when there is uncertainty about the most appropriate subsequent management.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"38 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unpicking the effects of FGF21 on longevity.","authors":"Claire Greenhill","doi":"10.1038/s41574-025-01147-3","DOIUrl":"https://doi.org/10.1038/s41574-025-01147-3","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"639 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cysteine deficiency induces rapid weight loss via adipose tissue browning","authors":"Olivia Tysoe","doi":"10.1038/s41574-025-01146-4","DOIUrl":"10.1038/s41574-025-01146-4","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"21 8","pages":"458-458"},"PeriodicalIF":31.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose tissue ageing: implications for metabolic health and lifespan.","authors":"Guan Wang,Anying Song,Qiong A Wang","doi":"10.1038/s41574-025-01142-8","DOIUrl":"https://doi.org/10.1038/s41574-025-01142-8","url":null,"abstract":"Adipose tissue, a pivotal player in whole-body energy homeostasis and insulin sensitivity, undergoes considerable remodelling throughout the ageing process, a facet that has garnered little attention until the past decade. This Review comprehensively summarizes the dynamic metabolic, cellular and functional changes that occur in white and thermogenic adipose tissue during distinct ageing stages, across different adipose tissue depots. We emphasize the influence of ageing on different cell types within adipose tissue, including adipocytes, adipocyte progenitors, immune cells and senescent cells, and their collective effect on adipose tissue function and systemic metabolism. We also decipher the correlation between adipose tissue ageing and prevalent age-related conditions such as metabolic dysfunction-associated fatty liver disease and cardiovascular diseases. Finally, the Review delves into the potential of current anti-ageing interventions to beneficially affect adipose tissue, encompassing caloric restriction, metformin, glucagon-like peptide 1 receptor agonists and senolytics. The discussion extends to the exploration of whether targeting adipose tissue through such interventions could emerge as a prominent therapeutic strategy for mitigating age-related diseases and enhancing the healthspan and lifespan of the ageing population.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"101 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticles help the spleen support pancreatic islet transplants","authors":"Senegal Carty","doi":"10.1038/s41574-025-01145-5","DOIUrl":"10.1038/s41574-025-01145-5","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"21 8","pages":"457-457"},"PeriodicalIF":31.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 1 diabetes mellitus prevention: present and future","authors":"Francisca L. Henriques, Irina Buckle, Josephine M. Forbes","doi":"10.1038/s41574-025-01128-6","DOIUrl":"https://doi.org/10.1038/s41574-025-01128-6","url":null,"abstract":"<p>Type 1 diabetes mellitus (T1DM) is a chronic disease with an increasing global incidence. The mortality associated with T1DM complications emphasizes the urgency of developing therapeutic strategies to prevent or delay the onset of T1DM. Historically, T1DM was solely described as a T cell-mediated disease. However, the role of β-cells as active participants in the immune-mediated damage is now well appreciated. Indeed, heterogeneity, vulnerability to stressors and the ability of β-cells to act as antigen-presenting cells has altered the perspective of what is necessary for effective disease prevention and ongoing β-cell preservation. Currently, teplizumab, an Fc-receptor non-binding humanized CD3-specific monoclonal antibody, is the only therapy approved by the FDA for the delay of T1DM onset. The intravenous administration, generalized immunosuppression and adverse effects mean that the transition to routine clinical practice is not without challenges. However, teplizumab could lead to the development of more accessible therapies. In this Review, we explore current and potential therapeutics for T1DM prevention. We offer alternative approaches, such as targeting the receptor for advanced glycation end products (RAGE). RAGE is a pattern recognition receptor that engages a wide range of ligands, including advanced glycation end products (AGEs; a family of molecules that includes the well described marker of long-term glucose concentrations, HbA_1c).</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"32 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyponatraemia in ageing","authors":"Sophie Monnerat, Mirjam Christ-Crain, Julie Refardt","doi":"10.1038/s41574-025-01138-4","DOIUrl":"https://doi.org/10.1038/s41574-025-01138-4","url":null,"abstract":"<p>Hyponatraemia is the most common electrolyte disorder in both inpatient and outpatient settings and mostly affects older adults, in whom intrinsic factors (such as chronic heart, liver or kidney diseases and malignancies) and extrinsic factors (such as polypharmacy and malnutrition) favouring hyponatraemia are highly prevalent. Importantly, its occurrence is expected to increase exponentially with global warming. Chronic hyponatraemia is associated with an increased risk of falling, osteoporosis and fractures, attention deficits, and even mortality. In the past two decades, a growing number of studies have suggested that correcting hyponatraemia improves clinical outcomes, outlining hyponatraemia management as a part of promoting healthy ageing. In addition, SGLT2 inhibitors and protein supplementation have been shown to be efficacious in treating hyponatraemia, both of which represent attractive and holistic treatment options in older adults. However, despite hyponatraemia being encountered in all medical specialties, its clinical burden is often overlooked, partly due to low awareness but also to low confidence in applying diagnostic and therapeutic algorithms. In this Review, we aim to depict the consequences of hyponatraemia, characterize the most common aetiologies in older individuals, and finally detail the diagnostic pathway as well as the benefits and limitations of the available treatment options.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"11 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing precision nutrition: bridging mechanistic insight and clinical implementation","authors":"Bruna R. da Silva, Lorraine Brennan, Maria Aderuza Horst, David S. Wishart, Carla M. Prado","doi":"10.1038/s41574-025-01141-9","DOIUrl":"https://doi.org/10.1038/s41574-025-01141-9","url":null,"abstract":"Precision nutrition is often used interchangeably with personalized nutrition, creating confusion and limiting progress. This Comment proposes a working definition of precision nutrition, outlines enabling frameworks such as artificial intelligence and highlights the need for consistent research standards and clinical validation to support and maximize precision nutrition’s potential in healthcare.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"44 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}