Pub Date : 2025-11-05DOI: 10.1038/s41574-025-01197-7
Chang-Hai Liu, Qing-Min Zeng, Won Kim, Seung Up Kim, Zobair M. Younossi, Giovanni Targher, Christopher D. Byrne, Christos S. Mantzoros, Phunchai Charatcharoenwitthaya, Isabelle Anne Leclercq, Manuel Romero-Gómez, Hong Tang, Ming-Hua Zheng
Metabolic dysfunction-associated steatotic liver disease (MASLD; previously known as non-alcoholic fatty liver disease) is the leading cause of chronic liver disease worldwide and is closely linked to the obesity epidemic. MASLD often coexists with sarcopenia, an age-related loss of muscle mass and muscle function. These conditions are closely connected, and metabolic syndrome and its associated metabolic factors have a crucial role in their relationship. Metabolic syndrome considerably affects the risk and progression of MASLD and sarcopenia and promotes their development through various mechanisms. This Review explores the epidemiological link between MASLD and sarcopenia and the effect of metabolic syndrome and its components on both conditions, summarizing current treatment strategies and emerging evidence. To effectively manage both MASLD and sarcopenia, it is crucial to incorporate the five metabolic risk factors of metabolic syndrome into risk assessment and treatment strategies. Future research should continue to investigate the mechanisms linking metabolic syndrome, MASLD and sarcopenia. Establishing standardized definitions of sarcopenia for patients with MASLD and developing personalized treatment strategies through precision medicine will improve diagnosis, interventions and overall patient outcomes. There is growing recognition of the metabolic links between metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia and the need to take these links into account when diagnosing and treating these two diseases. This Review covers connections between MASLD, sarcopenia and metabolic syndrome and discusses how care for patients affected by these diseases is evolving.
{"title":"Sarcopenia and MASLD: novel insights and the future","authors":"Chang-Hai Liu, Qing-Min Zeng, Won Kim, Seung Up Kim, Zobair M. Younossi, Giovanni Targher, Christopher D. Byrne, Christos S. Mantzoros, Phunchai Charatcharoenwitthaya, Isabelle Anne Leclercq, Manuel Romero-Gómez, Hong Tang, Ming-Hua Zheng","doi":"10.1038/s41574-025-01197-7","DOIUrl":"10.1038/s41574-025-01197-7","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD; previously known as non-alcoholic fatty liver disease) is the leading cause of chronic liver disease worldwide and is closely linked to the obesity epidemic. MASLD often coexists with sarcopenia, an age-related loss of muscle mass and muscle function. These conditions are closely connected, and metabolic syndrome and its associated metabolic factors have a crucial role in their relationship. Metabolic syndrome considerably affects the risk and progression of MASLD and sarcopenia and promotes their development through various mechanisms. This Review explores the epidemiological link between MASLD and sarcopenia and the effect of metabolic syndrome and its components on both conditions, summarizing current treatment strategies and emerging evidence. To effectively manage both MASLD and sarcopenia, it is crucial to incorporate the five metabolic risk factors of metabolic syndrome into risk assessment and treatment strategies. Future research should continue to investigate the mechanisms linking metabolic syndrome, MASLD and sarcopenia. Establishing standardized definitions of sarcopenia for patients with MASLD and developing personalized treatment strategies through precision medicine will improve diagnosis, interventions and overall patient outcomes. There is growing recognition of the metabolic links between metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia and the need to take these links into account when diagnosing and treating these two diseases. This Review covers connections between MASLD, sarcopenia and metabolic syndrome and discusses how care for patients affected by these diseases is evolving.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 3","pages":"139-152"},"PeriodicalIF":40.0,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440873","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}
Pub Date : 2025-10-31DOI: 10.1038/s41574-025-01196-8
Amir Moheet, Kevin J. Scully, Tasma Harindhanavudhi, Samantha Steinmetz-Wood, Heidi Guzman, Lesleann Hayward Story, Melissa S. Putman
Cystic fibrosis is a multisystem disorder caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, and is characterized by progressive pulmonary decline and exocrine pancreatic insufficiency. People with cystic fibrosis are at risk of multiple endocrine complications that can substantially increase morbidity and mortality, including cystic fibrosis-related diabetes (CFRD) and cystic fibrosis-related bone disease (CFBD). Children and adolescents with cystic fibrosis can also experience compromised growth and delayed puberty, although advances in clinical care and treatment have reduced rates of these complications. However, as people with cystic fibrosis live longer and healthier lives, new health challenges associated with these endocrine complications will become increasingly prevalent, including microvascular and macrovascular disease, obesity, metabolic syndrome, osteoporosis, fractures and earlier onset of perimenopause. In this Review, we summarize current knowledge on the epidemiology, pathophysiology, diagnosis and treatment of CFRD, CFBD, growth and puberty, hypogonadism and infertility, iatrogenic adrenal insufficiency and perimenopause in patients with cystic fibrosis. We also consider future research priorities in the field. Cystic fibrosis is associated with multiple endocrine complications, which are caused by systemic dysfunction of the cystic fibrosis transmembrane conductance regulator protein. In this Review, Moheet and colleagues describe these conditions, with particular emphasis on the effects of CFTR modulator therapy, as well as the challenges related to ageing in people with cystic fibrosis.
{"title":"The endocrine complications of cystic fibrosis","authors":"Amir Moheet, Kevin J. Scully, Tasma Harindhanavudhi, Samantha Steinmetz-Wood, Heidi Guzman, Lesleann Hayward Story, Melissa S. Putman","doi":"10.1038/s41574-025-01196-8","DOIUrl":"10.1038/s41574-025-01196-8","url":null,"abstract":"Cystic fibrosis is a multisystem disorder caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, and is characterized by progressive pulmonary decline and exocrine pancreatic insufficiency. People with cystic fibrosis are at risk of multiple endocrine complications that can substantially increase morbidity and mortality, including cystic fibrosis-related diabetes (CFRD) and cystic fibrosis-related bone disease (CFBD). Children and adolescents with cystic fibrosis can also experience compromised growth and delayed puberty, although advances in clinical care and treatment have reduced rates of these complications. However, as people with cystic fibrosis live longer and healthier lives, new health challenges associated with these endocrine complications will become increasingly prevalent, including microvascular and macrovascular disease, obesity, metabolic syndrome, osteoporosis, fractures and earlier onset of perimenopause. In this Review, we summarize current knowledge on the epidemiology, pathophysiology, diagnosis and treatment of CFRD, CFBD, growth and puberty, hypogonadism and infertility, iatrogenic adrenal insufficiency and perimenopause in patients with cystic fibrosis. We also consider future research priorities in the field. Cystic fibrosis is associated with multiple endocrine complications, which are caused by systemic dysfunction of the cystic fibrosis transmembrane conductance regulator protein. In this Review, Moheet and colleagues describe these conditions, with particular emphasis on the effects of CFTR modulator therapy, as well as the challenges related to ageing in people with cystic fibrosis.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 3","pages":"177-191"},"PeriodicalIF":40.0,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411518","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}
Pub Date : 2025-10-28DOI: 10.1038/s41574-025-01205-w
Peggy Lafuste, Frederic Relaix
Muscle regeneration relies on finely tuned hormonal signalling to regulate muscle stem cell activity. This Comment explores how anabolic, catabolic, metabolic and stress-related hormones influence muscle stem cell function and the muscle repair process, highlighting their therapeutic potential for combating ageing, injury and muscle-wasting diseases through targeted endocrine modulation.
{"title":"Endocrine control of skeletal muscle regeneration and clinical applications","authors":"Peggy Lafuste, Frederic Relaix","doi":"10.1038/s41574-025-01205-w","DOIUrl":"10.1038/s41574-025-01205-w","url":null,"abstract":"Muscle regeneration relies on finely tuned hormonal signalling to regulate muscle stem cell activity. This Comment explores how anabolic, catabolic, metabolic and stress-related hormones influence muscle stem cell function and the muscle repair process, highlighting their therapeutic potential for combating ageing, injury and muscle-wasting diseases through targeted endocrine modulation.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 1","pages":"5-6"},"PeriodicalIF":40.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381199","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}
Pub Date : 2025-10-28DOI: 10.1038/s41574-025-01204-x
Claire Greenhill
{"title":"The role of sweeteners in weight loss","authors":"Claire Greenhill","doi":"10.1038/s41574-025-01204-x","DOIUrl":"10.1038/s41574-025-01204-x","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 1","pages":"7-7"},"PeriodicalIF":40.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381148","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}
Pub Date : 2025-10-20DOI: 10.1038/s41574-025-01194-w
Dunya Tomic, Karen Walker-Bone, Tessa Keegel, Ella Zomer, Sophia Zoungas, Dianna J. Magliano
Work participation is beneficial for health. Diabetes mellitus is highly prevalent among adults, and although it poses a substantial healthcare cost burden, the true burden might be greater than is currently appreciated through effects on work participation. This Review summarizes the evidence regarding the effect of diabetes mellitus on paid employment. Several studies report increased risks of unemployment, early retirement and productivity loss among those with diabetes mellitus. The presence of diabetes mellitus complications and comorbidities probably further decreases work participation. Studies of workplace interventions demonstrate that work ability can be improved in people with diabetes mellitus. However, most existing research does not consider work characteristics (for example, type of work and working hours) in diabetes mellitus management. Whether diabetes mellitus itself increases occupational injury risk is unclear, with conflicting results reported. Most studies were cross-sectional and limited by use of self-reported diabetes mellitus and outcome measures, without consideration of the type of diabetes mellitus. Guidance on diabetes mellitus and employment has, to date, not been strongly grounded in evidence. Detailed research exploring factors implicated in work outcomes for people with diabetes mellitus, including age, sex, occupation and diabetes mellitus type, is needed to inform policy and support sustainable employment for those with diabetes mellitus. Participating in paid work is known to have beneficial effects; however, how diabetes mellitus might affect work participation is unclear. This Review outlines the available evidence and highlights research gaps.
{"title":"Diabetes mellitus and work participation","authors":"Dunya Tomic, Karen Walker-Bone, Tessa Keegel, Ella Zomer, Sophia Zoungas, Dianna J. Magliano","doi":"10.1038/s41574-025-01194-w","DOIUrl":"10.1038/s41574-025-01194-w","url":null,"abstract":"Work participation is beneficial for health. Diabetes mellitus is highly prevalent among adults, and although it poses a substantial healthcare cost burden, the true burden might be greater than is currently appreciated through effects on work participation. This Review summarizes the evidence regarding the effect of diabetes mellitus on paid employment. Several studies report increased risks of unemployment, early retirement and productivity loss among those with diabetes mellitus. The presence of diabetes mellitus complications and comorbidities probably further decreases work participation. Studies of workplace interventions demonstrate that work ability can be improved in people with diabetes mellitus. However, most existing research does not consider work characteristics (for example, type of work and working hours) in diabetes mellitus management. Whether diabetes mellitus itself increases occupational injury risk is unclear, with conflicting results reported. Most studies were cross-sectional and limited by use of self-reported diabetes mellitus and outcome measures, without consideration of the type of diabetes mellitus. Guidance on diabetes mellitus and employment has, to date, not been strongly grounded in evidence. Detailed research exploring factors implicated in work outcomes for people with diabetes mellitus, including age, sex, occupation and diabetes mellitus type, is needed to inform policy and support sustainable employment for those with diabetes mellitus. Participating in paid work is known to have beneficial effects; however, how diabetes mellitus might affect work participation is unclear. This Review outlines the available evidence and highlights research gaps.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 2","pages":"116-128"},"PeriodicalIF":40.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337342","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}
Pub Date : 2025-10-17DOI: 10.1038/s41574-025-01199-5
Christian Stoess, Janset Onyuru, Phillipp Hartmann, Hal M. Hoffman, Lori Broderick, Ariel E. Feldstein
Interleukin-18 (IL-18), a pyroptosis-related cytokine linking immunity and metabolism, regulates appetite, body weight and glucose homeostasis. IL-18 has paradoxical roles: its deficiency leads to obesity, whereas chronic signalling promotes liver fibrosis. Elevated in obesity and diabetes mellitus, IL-18 remains a compelling therapeutic target, with IL-18 binding protein showing anti-fibrotic potential in preclinical and early clinical studies.
{"title":"Interleukin-18 in obesity and obesity-related metabolic diseases","authors":"Christian Stoess, Janset Onyuru, Phillipp Hartmann, Hal M. Hoffman, Lori Broderick, Ariel E. Feldstein","doi":"10.1038/s41574-025-01199-5","DOIUrl":"10.1038/s41574-025-01199-5","url":null,"abstract":"Interleukin-18 (IL-18), a pyroptosis-related cytokine linking immunity and metabolism, regulates appetite, body weight and glucose homeostasis. IL-18 has paradoxical roles: its deficiency leads to obesity, whereas chronic signalling promotes liver fibrosis. Elevated in obesity and diabetes mellitus, IL-18 remains a compelling therapeutic target, with IL-18 binding protein showing anti-fibrotic potential in preclinical and early clinical studies.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 1","pages":"3-4"},"PeriodicalIF":40.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311382","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}
Pub Date : 2025-10-14DOI: 10.1038/s41574-025-01190-0
Jacqueline Jonklaas
The factors influencing the control of body weight are numerous and include many hormones. Even though levels of thyroid hormone might not always be the major factor affecting weight, in the sense that large changes in weight can occur despite a euthyroid state, there are notable changes in weight, appetite and body composition associated with excesses and deficiencies of thyroid hormone. Exploring the effect of thyroid hormone on weight is facilitated by studying the disease states of hypothyroidism and hyperthyroidism, the development and treatment of which can be associated with substantial changes in body weight. As is illustrated in the ensuing discussion, hypothyroidism is associated with modest increases in body weight and accompanying changes in body composition, with reversal of these alterations with its treatment. By contrast, hyperthyroidism can be accompanied by profound weight loss with reversal of the weight loss with restoration of euthyroidism. Using iatrogenic hyperthyroidism, whether during treatment for hypothyroidism or during off-label use in euthyroid individuals, has not proven to be an effective weight loss strategy.
{"title":"The complexity of the relationship between thyroid disease and body weight.","authors":"Jacqueline Jonklaas","doi":"10.1038/s41574-025-01190-0","DOIUrl":"https://doi.org/10.1038/s41574-025-01190-0","url":null,"abstract":"The factors influencing the control of body weight are numerous and include many hormones. Even though levels of thyroid hormone might not always be the major factor affecting weight, in the sense that large changes in weight can occur despite a euthyroid state, there are notable changes in weight, appetite and body composition associated with excesses and deficiencies of thyroid hormone. Exploring the effect of thyroid hormone on weight is facilitated by studying the disease states of hypothyroidism and hyperthyroidism, the development and treatment of which can be associated with substantial changes in body weight. As is illustrated in the ensuing discussion, hypothyroidism is associated with modest increases in body weight and accompanying changes in body composition, with reversal of these alterations with its treatment. By contrast, hyperthyroidism can be accompanied by profound weight loss with reversal of the weight loss with restoration of euthyroidism. Using iatrogenic hyperthyroidism, whether during treatment for hypothyroidism or during off-label use in euthyroid individuals, has not proven to be an effective weight loss strategy.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"91 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288497","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}
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