Nature Reviews Endocrinology最新文献

{"title":"Balancing weight and muscle loss in GLP1 receptor agonist therapy","authors":"Fabian Sanchis-Gomar, Ian J. Neeland, Carl J. Lavie","doi":"10.1038/s41574-025-01160-6","DOIUrl":"https://doi.org/10.1038/s41574-025-01160-6","url":null,"abstract":"Rapid weight loss with GLP1 receptor agonists can come at the cost of skeletal muscle, potentially undermining metabolic and functional outcomes. This Comment highlights emerging evidence and advocates for clinical strategies that prioritize muscle preservation to ensure the long-term success and safety of pharmacological weight management.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"26 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715298","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":"Highlights from ADA 85th Scientific Sessions","authors":"Senegal Carty","doi":"10.1038/s41574-025-01158-0","DOIUrl":"https://doi.org/10.1038/s41574-025-01158-0","url":null,"abstract":"<p>This year, from 20 June to 23 June, the American Diabetes Association’s (ADA’s) 85th Scientific Sessions brought over 11,000 participants to Chicago to share advances in research on diabetes mellitus.</p><p>The conference covered a great range of clinical, basic and translational research areas. One of the topics was how to maximize the utility of studies that investigate the interplay between genetics and environmental factors in the development and progression of diabetes mellitus. In the first symposium of the meeting, the ‘Pathway to Stop Diabetes’ symposium, Sara Tishkoff (University of Pennsylvania, USA) emphasized the importance of including participants with diverse ancestry in genome-wide association studies of diabetes mellitus. Tishkoff also highlighted the importance of comparing populations that are genetically similar, but have very different lifestyles, in the effort to distinguish between behavioural contributors to diabetes mellitus and hereditary factors that affect the risk of developing this disease.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"122 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144685048","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":"Combined amylin analogue and GLP1 receptor agonist therapies are highly promising for weight loss","authors":"Olivia Tysoe","doi":"10.1038/s41574-025-01156-2","DOIUrl":"https://doi.org/10.1038/s41574-025-01156-2","url":null,"abstract":"<p>The development of glucagon-like peptide 1 (GLP1) receptor agonists has led to unprecedented progress in the treatment of obesity. Highly successful medications for weight loss and type 2 diabetes mellitus (T2DM) have been developed by targeting the GLP1 receptor along with other, related receptors (for example, the dual GLP1 and GIP receptor agonist, tirzepatide). Now, another potential target for obesity therapeutics is showing promise: the amylin pathway.</p><p>REDEFINE 1 was a phase IIIa double-blind randomized controlled trial investigating the efficacy of CagriSema for weight loss in participants with obesity (BMI ≥ 30 kg/m²) or with overweight (BMI ≥ 27 kg/m²) and at least one obesity-related comorbidity (not diabetes mellitus). The trial involved a total of 3,417 participants: 2,108 received CagriSema, 302 received semaglutide monotherapy, 302 received cagrilintide monotherapy and 705 received placebo. “There were four randomization arms: co-administered CagriSema 2.4 mg/2.4 mg, the mono-components including both single agent (semaglutide) 2.4 mg and (cagrilintide) 2.4 mg, and placebo,” says Timothy Garvey, corresponding author of the REDEFINE 1 study. “It was important to show that the combination was more effective than either of the single agents alone and all were superior to placebo.”</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"5 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669704","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":"Language evolves — so can you","authors":"Sarah C. Westen, Laura M. Jacobsen","doi":"10.1038/s41574-025-01155-3","DOIUrl":"https://doi.org/10.1038/s41574-025-01155-3","url":null,"abstract":"As healthcare professionals, scientists and educators, our intent is to empower people affected by diabetes mellitus; however, if our language is stigmatizing, our impact might be disempowerment. If we do not choose our words with care, we risk undermining the very autonomy we seek to promote.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"52 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652281","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":"The role of GLP1 receptor agonists in adult-onset type 1 diabetes mellitus","authors":"Djordje S. Popovic, Theocharis Koufakis, Dimitrios Patoulias, Giuseppe Maltese, Nikolaos Papanas","doi":"10.1038/s41574-025-01154-4","DOIUrl":"https://doi.org/10.1038/s41574-025-01154-4","url":null,"abstract":"Adult-onset type 1 diabetes mellitus differs from the early onset form in terms of residual endogenous insulin secretion, comorbidities and baseline cardiorenal risk. Adjunct therapy with glucagon-like peptide 1 receptor agonists could offer benefits in this population of patients by preserving β-cell mass and function while also contributing to cardiorenal risk mitigation.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"24 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640354","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":"The role of ultra-processed food in obesity","authors":"Filippa Juul, Euridice Martinez-Steele, Niyati Parekh, Carlos A. Monteiro","doi":"10.1038/s41574-025-01143-7","DOIUrl":"https://doi.org/10.1038/s41574-025-01143-7","url":null,"abstract":"<p>The global increase in obesity has occurred in parallel to a dietary shift from traditional staple foods to ultra-processed foods (UPF), spurring scientific interest in UPF as a driver of the obesity pandemic. Herein, we summarize the current evidence regarding the role of UPF in obesity, with a specific focus on potential biological mechanisms. The literature strongly supports and corroborates ecological, epidemiological and mechanistic lines of research indicating that dietary patterns high in UPF promote overeating and increase the risk of overweight and obesity. Experimental evidence demonstrates that the soft texture, high energy density and hyperpalatable nutrient combinations of UPF facilitate excessive energy intakes by affecting ingestive behaviours, satiety signalling and food reward systems. Although not fully elucidated, it is plausible that several other UPF attributes (such as emulsifiers, non-nutritive sweeteners, acellular nutrients, and contaminants from processing and packaging materials) contribute to their obesogenic effects through a myriad of physiological pathways, including altered absorption kinetics, glycaemic response and the gut microbiota composition and function. To stem the global rise in obesity, multipronged policy efforts are needed to reduce UPF consumption and create health-promoting food systems.</p>","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"12 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622488","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":"Can obesity pharmacotherapy be used to manage male infertility?","authors":"Amy E. Morrison, Dimitris Papamargaritis, Channa N. Jayasena, Neelam Potdar, Thomas Yates, Gregory J. H. Biddle, Malak Hamza, Melanie J. Davies, Narendra L. Reddy","doi":"10.1038/s41574-025-01151-7","DOIUrl":"https://doi.org/10.1038/s41574-025-01151-7","url":null,"abstract":"Obesity-related subfertility is an increasingly recognized concern. Pharmacotherapies (particularly glucagon-like peptide&nbsp;1 receptor agonists and combination therapies), alongside lifestyle intervention, enable meaningful and sustainable weight loss in people with and without type&nbsp;2 diabetes mellitus. Weight loss can benefit sperm parameters, but the optimal amount and rate of weight loss requires further study.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"38 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622447","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":"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}