Pub Date : 2024-07-17DOI: 10.1038/s41574-024-01014-7
Silvia Marino, Teresita Bellido
Basic, translational and clinical research over the past few decades has provided new understanding on the mechanisms by which activation of the receptor of parathyroid hormone (parathyroid hormone 1 receptor (PTH1R)) regulates bone physiology and pathophysiology. A fundamental change in the field emerged upon the recognition that osteocytes, which are permanent residents of bone and the most abundant cells in bone, are targets of the actions of natural and synthetic ligands of PTH1R (parathyroid hormone and abaloparatide, respectively), and that these cells drive essential actions related to bone remodelling. Among the numerous genes regulated by PTH1R in osteocytes, SOST (which encodes sclerostin, the WNT signalling antagonist and inhibitor of bone formation) has a critical role in bone homeostasis and changes in its expression are associated with several bone pathologies. The bone fragility syndrome induced by diabetes mellitus is accompanied by increased osteocyte apoptosis and changes in the expression of osteocytic genes, including SOST. This Review will discuss advances in our knowledge of the role of osteocytes in PTH1R signalling and the new opportunities to restore bone health in diabetes mellitus by targeting the osteocytic PTH1R–sclerostin axis. This article reviews the role of the parathyroid hormone 1 receptor (PTH1R) pathway in bone homeostasis and of osteocytes as mechanosensors and drivers of bone remodelling. It will also discuss how the PTH1R–sclerostin axis can be harnessed for the treatment of bone disease induced by diabetes mellitus.
{"title":"PTH receptor signalling, osteocytes and bone disease induced by diabetes mellitus","authors":"Silvia Marino, Teresita Bellido","doi":"10.1038/s41574-024-01014-7","DOIUrl":"10.1038/s41574-024-01014-7","url":null,"abstract":"Basic, translational and clinical research over the past few decades has provided new understanding on the mechanisms by which activation of the receptor of parathyroid hormone (parathyroid hormone 1 receptor (PTH1R)) regulates bone physiology and pathophysiology. A fundamental change in the field emerged upon the recognition that osteocytes, which are permanent residents of bone and the most abundant cells in bone, are targets of the actions of natural and synthetic ligands of PTH1R (parathyroid hormone and abaloparatide, respectively), and that these cells drive essential actions related to bone remodelling. Among the numerous genes regulated by PTH1R in osteocytes, SOST (which encodes sclerostin, the WNT signalling antagonist and inhibitor of bone formation) has a critical role in bone homeostasis and changes in its expression are associated with several bone pathologies. The bone fragility syndrome induced by diabetes mellitus is accompanied by increased osteocyte apoptosis and changes in the expression of osteocytic genes, including SOST. This Review will discuss advances in our knowledge of the role of osteocytes in PTH1R signalling and the new opportunities to restore bone health in diabetes mellitus by targeting the osteocytic PTH1R–sclerostin axis. This article reviews the role of the parathyroid hormone 1 receptor (PTH1R) pathway in bone homeostasis and of osteocytes as mechanosensors and drivers of bone remodelling. It will also discuss how the PTH1R–sclerostin axis can be harnessed for the treatment of bone disease induced by diabetes mellitus.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 11","pages":"661-672"},"PeriodicalIF":31.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141631315","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 : 2024-07-15DOI: 10.1038/s41574-024-01012-9
Emma Börgeson, Saeideh Tavajoh, Stephan Lange, Niels Jessen
To tackle the burden of obesity-induced cardiometabolic disease, the scientific community relies on accurate and reproducible adiposity measurements in the clinic. These measurements guide our understanding of underlying biological mechanisms and clinical outcomes of human trials. However, measuring adiposity and adipose tissue distribution in a clinical setting can be challenging, and different measurement methods pose important limitations. BMI is a simple and high-throughput measurement, but it is associated relatively poorly with clinical outcomes when compared with waist-to-hip and sagittal abdominal diameter measurements. Body composition measurements by dual energy X-ray absorptiometry or MRI scans would be ideal due to their high accuracy, but are not high-throughput. Another important consideration is that adiposity measurements vary between men and women, between adults and children, and between people of different ethnic backgrounds. In this Perspective article, we discuss how these critical challenges can affect our interpretation of research data in the field of obesity and the design and implementation of clinical guidelines. Accurate measurement of adiposity and adipose tissue distribution is essential for the treatment of obesity and cardiometabolic disease, but can often prove challenging. This Perspective discusses the advantages and disadvantages of different methods of assessing adiposity in clinical settings.
为了解决肥胖引起的心脏代谢疾病的负担，科学界依赖于临床上准确和可重复的脂肪测量。这些测量结果指导我们了解人体试验的潜在生物机制和临床结果。然而，在临床环境中测量脂肪含量和脂肪组织分布具有挑战性，而且不同的测量方法也存在重要的局限性。体重指数是一种简单、高通量的测量方法，但与腰臀围和腹部矢状径的测量方法相比，体重指数与临床结果的相关性相对较低。通过双能 X 射线吸收测量法或核磁共振成像扫描测量身体成分因其准确性高而成为理想的方法，但其测量量并不高。另一个重要的考虑因素是，脂肪测量结果在男女之间、成人和儿童之间以及不同种族背景的人群之间存在差异。在这篇 "视角 "文章中，我们将讨论这些关键挑战会如何影响我们对肥胖领域研究数据的解读以及临床指南的设计和实施。
{"title":"The challenges of assessing adiposity in a clinical setting","authors":"Emma Börgeson, Saeideh Tavajoh, Stephan Lange, Niels Jessen","doi":"10.1038/s41574-024-01012-9","DOIUrl":"10.1038/s41574-024-01012-9","url":null,"abstract":"To tackle the burden of obesity-induced cardiometabolic disease, the scientific community relies on accurate and reproducible adiposity measurements in the clinic. These measurements guide our understanding of underlying biological mechanisms and clinical outcomes of human trials. However, measuring adiposity and adipose tissue distribution in a clinical setting can be challenging, and different measurement methods pose important limitations. BMI is a simple and high-throughput measurement, but it is associated relatively poorly with clinical outcomes when compared with waist-to-hip and sagittal abdominal diameter measurements. Body composition measurements by dual energy X-ray absorptiometry or MRI scans would be ideal due to their high accuracy, but are not high-throughput. Another important consideration is that adiposity measurements vary between men and women, between adults and children, and between people of different ethnic backgrounds. In this Perspective article, we discuss how these critical challenges can affect our interpretation of research data in the field of obesity and the design and implementation of clinical guidelines. Accurate measurement of adiposity and adipose tissue distribution is essential for the treatment of obesity and cardiometabolic disease, but can often prove challenging. This Perspective discusses the advantages and disadvantages of different methods of assessing adiposity in clinical settings.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 10","pages":"615-626"},"PeriodicalIF":31.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618353","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 : 2024-07-09DOI: 10.1038/s41574-024-01018-3
Fadi Khalaf, Zachary Ricciuti, Dalia Barayan, Stephanie Wojtowicz-Piotrowski, Marc G. Jeschke
Thermal injuries trigger stress-induced endocrine responses that are critical for survival. With age, these responses falter, which results in an inability to combat burn-induced dysfunction and greatly increased mortality. Current knowledge about the post-burn endocrine response in older adults is sparse, which leaves therapeutic gaps for this vulnerable and expanding demographic.
{"title":"Post-burn endocrine–immune dynamics and ageing considerations","authors":"Fadi Khalaf, Zachary Ricciuti, Dalia Barayan, Stephanie Wojtowicz-Piotrowski, Marc G. Jeschke","doi":"10.1038/s41574-024-01018-3","DOIUrl":"10.1038/s41574-024-01018-3","url":null,"abstract":"Thermal injuries trigger stress-induced endocrine responses that are critical for survival. With age, these responses falter, which results in an inability to combat burn-induced dysfunction and greatly increased mortality. Current knowledge about the post-burn endocrine response in older adults is sparse, which leaves therapeutic gaps for this vulnerable and expanding demographic.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 10","pages":"567-568"},"PeriodicalIF":31.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563833","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 : 2024-07-08DOI: 10.1038/s41574-024-01019-2
Olivia Tysoe
{"title":"Artemisinins as a promising treatment for polycystic ovary syndrome","authors":"Olivia Tysoe","doi":"10.1038/s41574-024-01019-2","DOIUrl":"10.1038/s41574-024-01019-2","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 9","pages":"508-508"},"PeriodicalIF":31.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559194","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 : 2024-07-01DOI: 10.1038/s41574-024-01015-6
Shimona Starling
{"title":"A trio of trials on hormone receptor agonists for MASLD","authors":"Shimona Starling","doi":"10.1038/s41574-024-01015-6","DOIUrl":"10.1038/s41574-024-01015-6","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 8","pages":"445-445"},"PeriodicalIF":31.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476994","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 : 2024-06-27DOI: 10.1038/s41574-024-01008-5
Matthias B. Schulze, Norbert Stefan
The concept of metabolic health, particularly in obesity, has attracted a lot of attention in the scientific community, and is being increasingly used to determine the risk of cardiovascular diseases and diabetes mellitus-related complications. This Review assesses the current understanding of metabolically healthy obesity (MHO). First, we present the historical evolution of the concept. Second, we discuss the evidence for and against its existence, the usage of different definitions of MHO over the years and the efforts made to provide novel definitions of MHO. Third, we highlight epidemiological data with regard to cardiovascular risk in MHO, which is estimated to be moderately elevated using widely used definitions of MHO when compared with individuals with metabolically healthy normal weight, but potentially not elevated using a novel definition of MHO. Fourth, we discuss novel findings about the physiological mechanisms involved in MHO and how such knowledge helps to identify and characterize both people with MHO and those with metabolically unhealthy normal weight. Finally, we address how the concept of MHO can be used for risk stratification and treatment in clinical practice. This Review discusses the current understanding of the concept of metabolically healthy obesity (MHO), the challenges in defining MHO and how the MHO concept can be used to improve the prevention and treatment of cardiometabolic disease.
{"title":"Metabolically healthy obesity: from epidemiology and mechanisms to clinical implications","authors":"Matthias B. Schulze, Norbert Stefan","doi":"10.1038/s41574-024-01008-5","DOIUrl":"10.1038/s41574-024-01008-5","url":null,"abstract":"The concept of metabolic health, particularly in obesity, has attracted a lot of attention in the scientific community, and is being increasingly used to determine the risk of cardiovascular diseases and diabetes mellitus-related complications. This Review assesses the current understanding of metabolically healthy obesity (MHO). First, we present the historical evolution of the concept. Second, we discuss the evidence for and against its existence, the usage of different definitions of MHO over the years and the efforts made to provide novel definitions of MHO. Third, we highlight epidemiological data with regard to cardiovascular risk in MHO, which is estimated to be moderately elevated using widely used definitions of MHO when compared with individuals with metabolically healthy normal weight, but potentially not elevated using a novel definition of MHO. Fourth, we discuss novel findings about the physiological mechanisms involved in MHO and how such knowledge helps to identify and characterize both people with MHO and those with metabolically unhealthy normal weight. Finally, we address how the concept of MHO can be used for risk stratification and treatment in clinical practice. This Review discusses the current understanding of the concept of metabolically healthy obesity (MHO), the challenges in defining MHO and how the MHO concept can be used to improve the prevention and treatment of cardiometabolic disease.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 11","pages":"633-646"},"PeriodicalIF":31.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462556","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 : 2024-06-26DOI: 10.1038/s41574-024-01013-8
Claire Greenhill
{"title":"Progestin production by the gut microbiota","authors":"Claire Greenhill","doi":"10.1038/s41574-024-01013-8","DOIUrl":"10.1038/s41574-024-01013-8","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 8","pages":"446-446"},"PeriodicalIF":31.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453118","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 : 2024-06-21DOI: 10.1038/s41574-024-01003-w
Marian E. Ludgate, Giulia Masetti, Paula Soares
Disorders of the thyroid gland are common, more prevalent in women than in men, and range from inflammatory to neoplastic lesions. Autoimmune thyroid diseases (AITD) affect 2–5% of the population, while thyroid cancer is the most frequent endocrine malignancy. Treatment for AITD is still restricted to management rather than prevention or cure. Progress has been made in identifying genetic variants that predispose to AITD and thyroid cancer, but the increasing prevalence of all thyroid disorders indicates that factors other than genes are involved. The gut microbiota, which begins to develop before birth, is highly sensitive to diet and the environment, providing a potential mechanism for non-communicable diseases to become communicable. Its functions extend beyond maintenance of gut integrity: the gut microbiota regulates the immune system, contributes to thyroid hormone metabolism and can generate or catabolize carcinogens, all of which are relevant to AITD and thyroid cancer. Observational and interventional studies in animal models support a role for the gut microbiota in AITD, which has been confirmed in some reports from human cohorts, although considerable geographic variation is apparent. Reports of a role for the microbiota in thyroid cancer are more limited, but evidence supports a relationship between gut dysbiosis and thyroid cancer. The gut microbiota has been implicated in the increasing prevalence of thyroid disorders, including autoimmune thyroid diseases and thyroid cancers, through its effects on gut integrity, immune regulation and thyroid hormone metabolism, as outlined in this article.
{"title":"The relationship between the gut microbiota and thyroid disorders","authors":"Marian E. Ludgate, Giulia Masetti, Paula Soares","doi":"10.1038/s41574-024-01003-w","DOIUrl":"10.1038/s41574-024-01003-w","url":null,"abstract":"Disorders of the thyroid gland are common, more prevalent in women than in men, and range from inflammatory to neoplastic lesions. Autoimmune thyroid diseases (AITD) affect 2–5% of the population, while thyroid cancer is the most frequent endocrine malignancy. Treatment for AITD is still restricted to management rather than prevention or cure. Progress has been made in identifying genetic variants that predispose to AITD and thyroid cancer, but the increasing prevalence of all thyroid disorders indicates that factors other than genes are involved. The gut microbiota, which begins to develop before birth, is highly sensitive to diet and the environment, providing a potential mechanism for non-communicable diseases to become communicable. Its functions extend beyond maintenance of gut integrity: the gut microbiota regulates the immune system, contributes to thyroid hormone metabolism and can generate or catabolize carcinogens, all of which are relevant to AITD and thyroid cancer. Observational and interventional studies in animal models support a role for the gut microbiota in AITD, which has been confirmed in some reports from human cohorts, although considerable geographic variation is apparent. Reports of a role for the microbiota in thyroid cancer are more limited, but evidence supports a relationship between gut dysbiosis and thyroid cancer. The gut microbiota has been implicated in the increasing prevalence of thyroid disorders, including autoimmune thyroid diseases and thyroid cancers, through its effects on gut integrity, immune regulation and thyroid hormone metabolism, as outlined in this article.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 9","pages":"511-525"},"PeriodicalIF":31.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435844","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 : 2024-06-19DOI: 10.1038/s41574-024-01011-w
Denise D. Belsham
{"title":"Mind the (human-based new approach methodology) gap!","authors":"Denise D. Belsham","doi":"10.1038/s41574-024-01011-w","DOIUrl":"10.1038/s41574-024-01011-w","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 9","pages":"509-509"},"PeriodicalIF":31.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425231","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 : 2024-06-19DOI: 10.1038/s41574-024-01009-4
Krista A. Varady, Shuhao Lin, Vanessa M. Oddo, Sofia Cienfuegos
Despite the mounting evidence supporting the use of intermittent fasting as a safe and effective weight loss intervention, many myths about fasting persist in popular culture. Here, we review some common beliefs about intermittent fasting that are not supported by scientific evidence.
{"title":"Debunking the myths of intermittent fasting","authors":"Krista A. Varady, Shuhao Lin, Vanessa M. Oddo, Sofia Cienfuegos","doi":"10.1038/s41574-024-01009-4","DOIUrl":"10.1038/s41574-024-01009-4","url":null,"abstract":"Despite the mounting evidence supporting the use of intermittent fasting as a safe and effective weight loss intervention, many myths about fasting persist in popular culture. Here, we review some common beliefs about intermittent fasting that are not supported by scientific evidence.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 9","pages":"503-504"},"PeriodicalIF":31.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425336","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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