Pub Date : 2024-10-22DOI: 10.1038/s41574-024-01051-2
Claire Greenhill
{"title":"The complex effects of dietary restriction on longevity and health","authors":"Claire Greenhill","doi":"10.1038/s41574-024-01051-2","DOIUrl":"10.1038/s41574-024-01051-2","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 12","pages":"697-697"},"PeriodicalIF":31.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452506","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 : 2024-10-08DOI: 10.1038/s41574-024-01048-x
Senegal Carty
{"title":"Signals from the dorsal motor nucleus of the vagus promote jejunal fat absorption","authors":"Senegal Carty","doi":"10.1038/s41574-024-01048-x","DOIUrl":"10.1038/s41574-024-01048-x","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 12","pages":"698-698"},"PeriodicalIF":31.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384236","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 : 2024-10-08DOI: 10.1038/s41574-024-01039-y
Seppe Melis, Dana Trompet, Andrei S. Chagin, Christa Maes
Skeletal stem cells (SSCs) and related progenitors with osteogenic potential, collectively termed skeletal stem and/or progenitor cells (SSPCs), are crucial for providing osteoblasts for bone formation during homeostatic tissue turnover and fracture repair. Besides mediating normal bone physiology, they also have important roles in various metabolic bone diseases, including osteoporosis. SSPCs are of tremendous interest because they represent prime future targets for osteoanabolic therapies and bone regenerative medicine. Remarkable progress has been made in characterizing various SSC and SSPC populations in postnatal bone. SSPCs exist in the periosteum and within the bone marrow stroma, including subsets localizing around arteriolar and sinusoidal blood vessels; they can display osteogenic, chondrogenic, adipogenic and/or fibroblastic potential, and exert critical haematopoiesis-supportive functions. However, much remains to be clarified. By the current markers, bona fide SSCs are commonly contained within broader SSPC populations characterized by considerable heterogeneity and overlap, whose common versus specific functions in health and disease have not been fully unravelled. Here, we review the present knowledge of the identity, fates and relationships of SSPC populations in the postnatal bone environment, their contributions to bone maintenance, the changes observed upon ageing, and the effect of metabolic diseases such as osteoporosis and diabetes mellitus. Various populations of skeletal stem and progenitor cells (SSPCs) exist within the native skeletal environments of humans and mice, with complex roles in the maintenance of bone tissue. This Review discusses the current state of knowledge of the identity and roles of SSPCs in skeletal health, disease and ageing.
{"title":"Skeletal stem and progenitor cells in bone physiology, ageing and disease","authors":"Seppe Melis, Dana Trompet, Andrei S. Chagin, Christa Maes","doi":"10.1038/s41574-024-01039-y","DOIUrl":"10.1038/s41574-024-01039-y","url":null,"abstract":"Skeletal stem cells (SSCs) and related progenitors with osteogenic potential, collectively termed skeletal stem and/or progenitor cells (SSPCs), are crucial for providing osteoblasts for bone formation during homeostatic tissue turnover and fracture repair. Besides mediating normal bone physiology, they also have important roles in various metabolic bone diseases, including osteoporosis. SSPCs are of tremendous interest because they represent prime future targets for osteoanabolic therapies and bone regenerative medicine. Remarkable progress has been made in characterizing various SSC and SSPC populations in postnatal bone. SSPCs exist in the periosteum and within the bone marrow stroma, including subsets localizing around arteriolar and sinusoidal blood vessels; they can display osteogenic, chondrogenic, adipogenic and/or fibroblastic potential, and exert critical haematopoiesis-supportive functions. However, much remains to be clarified. By the current markers, bona fide SSCs are commonly contained within broader SSPC populations characterized by considerable heterogeneity and overlap, whose common versus specific functions in health and disease have not been fully unravelled. Here, we review the present knowledge of the identity, fates and relationships of SSPC populations in the postnatal bone environment, their contributions to bone maintenance, the changes observed upon ageing, and the effect of metabolic diseases such as osteoporosis and diabetes mellitus. Various populations of skeletal stem and progenitor cells (SSPCs) exist within the native skeletal environments of humans and mice, with complex roles in the maintenance of bone tissue. This Review discusses the current state of knowledge of the identity and roles of SSPCs in skeletal health, disease and ageing.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"21 3","pages":"135-153"},"PeriodicalIF":31.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384877","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 : 2024-09-25DOI: 10.1038/s41574-024-01037-0
Rhonda D. Kineman, Mercedes del Rio-Moreno, David J. Waxman
Metabolic dysfunction-associated steatotic liver disease (MASLD; also known as nonalcoholic fatty liver disease) is a chronic condition associated with metabolic syndrome, a group of conditions that includes obesity, insulin resistance, hyperlipidaemia and cardiovascular disease. Primary growth hormone (GH) deficiency is associated with MASLD, and the decline in circulating levels of GH with weight gain might contribute to the development of MASLD. Raising endogenous GH secretion or administering GH replacement therapy in the context of MASLD enhances insulin-like growth factor 1 (IGF1) production and reduces steatosis and the severity of liver injury. GH and IGF1 indirectly control MASLD progression by regulating systemic metabolic function. Evidence supports the proposal that GH and IGF1 also have a direct role in regulating liver metabolism and health. This Review focuses on how GH acts on the hepatocyte in a sex-dependent manner to limit lipid accumulation, reduce stress, and promote survival and regeneration. In addition, we discuss how GH and IGF1 might regulate non-parenchymal cells of the liver to control inflammation and fibrosis, which have a major effect on hepatocyte survival and regeneration. Development of a better understanding of how GH and IGF1 coordinate the functions of specific, individual liver cell types might provide insight into the aetiology of MASLD initiation and progression and suggest novel approaches for the treatment of MASLD. This Review discusses the roles of growth hormone (GH) and insulin-like growth factor 1 (IGF1) signalling in reducing the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Sex-dependent differences in MASLD susceptibility and the effects of GH and IGF1 on hepatocytes and non-parenchymal cells are considered.
{"title":"Liver-specific actions of GH and IGF1 that protect against MASLD","authors":"Rhonda D. Kineman, Mercedes del Rio-Moreno, David J. Waxman","doi":"10.1038/s41574-024-01037-0","DOIUrl":"10.1038/s41574-024-01037-0","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD; also known as nonalcoholic fatty liver disease) is a chronic condition associated with metabolic syndrome, a group of conditions that includes obesity, insulin resistance, hyperlipidaemia and cardiovascular disease. Primary growth hormone (GH) deficiency is associated with MASLD, and the decline in circulating levels of GH with weight gain might contribute to the development of MASLD. Raising endogenous GH secretion or administering GH replacement therapy in the context of MASLD enhances insulin-like growth factor 1 (IGF1) production and reduces steatosis and the severity of liver injury. GH and IGF1 indirectly control MASLD progression by regulating systemic metabolic function. Evidence supports the proposal that GH and IGF1 also have a direct role in regulating liver metabolism and health. This Review focuses on how GH acts on the hepatocyte in a sex-dependent manner to limit lipid accumulation, reduce stress, and promote survival and regeneration. In addition, we discuss how GH and IGF1 might regulate non-parenchymal cells of the liver to control inflammation and fibrosis, which have a major effect on hepatocyte survival and regeneration. Development of a better understanding of how GH and IGF1 coordinate the functions of specific, individual liver cell types might provide insight into the aetiology of MASLD initiation and progression and suggest novel approaches for the treatment of MASLD. This Review discusses the roles of growth hormone (GH) and insulin-like growth factor 1 (IGF1) signalling in reducing the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Sex-dependent differences in MASLD susceptibility and the effects of GH and IGF1 on hepatocytes and non-parenchymal cells are considered.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"21 2","pages":"105-117"},"PeriodicalIF":31.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317017","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 : 2024-09-23DOI: 10.1038/s41574-024-01036-1
Marysia Placzek, Kavitha Chinnaiya, Dong Won Kim, Seth Blackshaw
The tuberal hypothalamus regulates a range of crucial physiological processes, including energy homeostasis and metabolism. In this Review, we explore the intricate molecular mechanisms and signalling pathways that control the development of the tuberal hypothalamus, focusing on aspects that shape metabolic outcomes. Major developmental events are discussed in the context of their effect on the establishment of both functional hypothalamic neuronal circuits and brain–body interfaces that are pivotal to the control of metabolism. Emerging evidence indicates that aberrations in molecular pathways during tuberal hypothalamic development contribute to metabolic dysregulation. Understanding the molecular underpinnings of tuberal hypothalamic development provides a comprehensive view of neurodevelopmental processes and offers a promising avenue for future targeted interventions to prevent and treat metabolic disorders. The tuberal hypothalamus regulates a range of crucial physiological processes, including energy homeostasis and metabolism. This Review discusses the intricate molecular mechanisms and signalling pathways that control the development of the tuberal hypothalamus, focusing on aspects that shape metabolic outcomes.
{"title":"Control of tuberal hypothalamic development and its implications in metabolic disorders","authors":"Marysia Placzek, Kavitha Chinnaiya, Dong Won Kim, Seth Blackshaw","doi":"10.1038/s41574-024-01036-1","DOIUrl":"10.1038/s41574-024-01036-1","url":null,"abstract":"The tuberal hypothalamus regulates a range of crucial physiological processes, including energy homeostasis and metabolism. In this Review, we explore the intricate molecular mechanisms and signalling pathways that control the development of the tuberal hypothalamus, focusing on aspects that shape metabolic outcomes. Major developmental events are discussed in the context of their effect on the establishment of both functional hypothalamic neuronal circuits and brain–body interfaces that are pivotal to the control of metabolism. Emerging evidence indicates that aberrations in molecular pathways during tuberal hypothalamic development contribute to metabolic dysregulation. Understanding the molecular underpinnings of tuberal hypothalamic development provides a comprehensive view of neurodevelopmental processes and offers a promising avenue for future targeted interventions to prevent and treat metabolic disorders. The tuberal hypothalamus regulates a range of crucial physiological processes, including energy homeostasis and metabolism. This Review discusses the intricate molecular mechanisms and signalling pathways that control the development of the tuberal hypothalamus, focusing on aspects that shape metabolic outcomes.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"21 2","pages":"118-130"},"PeriodicalIF":31.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276914","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 : 2024-09-23DOI: 10.1038/s41574-024-01035-2
Kylie D. Hesketh, Miaobing Zheng, Karen J. Campbell
The prevalence of obesity increases with age but is apparent even in early life. Early childhood is a critical period for development that is known to influence future health. Even so, the focus on obesity in this phase, and the factors that affect the development of obesity, has only emerged over the past two decades. Furthermore, there is a paucity of iterative work in this area that would move the field forward. Obesity is a complex condition involving the interplay of multiple influences at different levels: the individual and biological level, the sociocultural level, and the environmental and system levels. This Review provides a brief overview of the evidence for these factors with a focus on aspects specific to early life. By spotlighting the complex web of interactions between the broad range of influences, both causal and risk markers, we highlight the complex nature of the condition. Much work in the early life field remains observational and many of the intervention studies are limited by a focus on single influences and a disjointed approach to solutions. Yet the complexity of obesity necessitates coordinated multi-focused solutions and joined-up action across the first 2,000 days from conception, and beyond. The increasing prevalence of obesity is influenced by individual, biological, sociocultural and environmental factors; and many are already apparent in early childhood. This Review highlights the need for coordinated, multifaceted interventions across a child’s first 2,000 days to address this complex condition effectively.
{"title":"Early life factors that affect obesity and the need for complex solutions","authors":"Kylie D. Hesketh, Miaobing Zheng, Karen J. Campbell","doi":"10.1038/s41574-024-01035-2","DOIUrl":"10.1038/s41574-024-01035-2","url":null,"abstract":"The prevalence of obesity increases with age but is apparent even in early life. Early childhood is a critical period for development that is known to influence future health. Even so, the focus on obesity in this phase, and the factors that affect the development of obesity, has only emerged over the past two decades. Furthermore, there is a paucity of iterative work in this area that would move the field forward. Obesity is a complex condition involving the interplay of multiple influences at different levels: the individual and biological level, the sociocultural level, and the environmental and system levels. This Review provides a brief overview of the evidence for these factors with a focus on aspects specific to early life. By spotlighting the complex web of interactions between the broad range of influences, both causal and risk markers, we highlight the complex nature of the condition. Much work in the early life field remains observational and many of the intervention studies are limited by a focus on single influences and a disjointed approach to solutions. Yet the complexity of obesity necessitates coordinated multi-focused solutions and joined-up action across the first 2,000 days from conception, and beyond. The increasing prevalence of obesity is influenced by individual, biological, sociocultural and environmental factors; and many are already apparent in early childhood. This Review highlights the need for coordinated, multifaceted interventions across a child’s first 2,000 days to address this complex condition effectively.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"21 1","pages":"31-44"},"PeriodicalIF":31.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276905","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 : 2024-09-23DOI: 10.1038/s41574-024-01032-5
Joanne Lysaght, Melissa J. Conroy
Epidemiology studies have demonstrated a clear association between obesity and the development of several distinct malignancies, with excessive visceral adiposity being an increasingly prevalent feature in patients with cancer presenting for therapeutic intervention. Clinical trials and meta-analyses have helped to inform effective and safe dosing of traditional systemically administered anticancer agents in adult patients with cancer and obesity, but there remains much debate not only regarding the effect of obesity on the more novel targeted molecular and immune-based therapies, but also about how obesity is best defined and measured clinically. Low muscle mass is associated with poor outcomes in cancer, and body composition studies using biochemical and imaging modalities are helping to fully delineate the importance of both obesity and sarcopenia in clinical outcomes; such studies might also go some way to explaining how obesity can paradoxically be associated with favourable clinical outcomes in certain cancers. As the cancer survivorship period increases and the duration of anticancer treatment lengthens, this Review highlights the challenges facing appropriate treatment selection and emphasizes how a multidisciplinary approach is warranted to manage weight and skeletal muscle loss during and after cancer treatment. This Review outlines the multifaceted influence of obesity on cancer treatment effectiveness and associated toxicities, and explores complex issues, such as body composition and the obesity paradox, that link obesity with outcomes for patients with cancer.
{"title":"The multifactorial effect of obesity on the effectiveness and outcomes of cancer therapies","authors":"Joanne Lysaght, Melissa J. Conroy","doi":"10.1038/s41574-024-01032-5","DOIUrl":"10.1038/s41574-024-01032-5","url":null,"abstract":"Epidemiology studies have demonstrated a clear association between obesity and the development of several distinct malignancies, with excessive visceral adiposity being an increasingly prevalent feature in patients with cancer presenting for therapeutic intervention. Clinical trials and meta-analyses have helped to inform effective and safe dosing of traditional systemically administered anticancer agents in adult patients with cancer and obesity, but there remains much debate not only regarding the effect of obesity on the more novel targeted molecular and immune-based therapies, but also about how obesity is best defined and measured clinically. Low muscle mass is associated with poor outcomes in cancer, and body composition studies using biochemical and imaging modalities are helping to fully delineate the importance of both obesity and sarcopenia in clinical outcomes; such studies might also go some way to explaining how obesity can paradoxically be associated with favourable clinical outcomes in certain cancers. As the cancer survivorship period increases and the duration of anticancer treatment lengthens, this Review highlights the challenges facing appropriate treatment selection and emphasizes how a multidisciplinary approach is warranted to manage weight and skeletal muscle loss during and after cancer treatment. This Review outlines the multifaceted influence of obesity on cancer treatment effectiveness and associated toxicities, and explores complex issues, such as body composition and the obesity paradox, that link obesity with outcomes for patients with cancer.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 12","pages":"701-714"},"PeriodicalIF":31.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276872","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 : 2024-09-20DOI: 10.1038/s41574-024-01043-2
Pamela Fischer-Posovszky, Julia Zinngrebe
Brown adipocytes are increasingly recognized as a promising therapeutic target for metabolic disorders. Research published in Advanced Science now presents evidence that these cells might also be useful for leukaemia therapy. The study demonstrates that activation of brown adipocytes deprives leukaemia cells of glucose, which reveals a potential new avenue for leukaemia treatment.
{"title":"Brown adipose tissue fights the battle against leukaemia","authors":"Pamela Fischer-Posovszky, Julia Zinngrebe","doi":"10.1038/s41574-024-01043-2","DOIUrl":"10.1038/s41574-024-01043-2","url":null,"abstract":"Brown adipocytes are increasingly recognized as a promising therapeutic target for metabolic disorders. Research published in Advanced Science now presents evidence that these cells might also be useful for leukaemia therapy. The study demonstrates that activation of brown adipocytes deprives leukaemia cells of glucose, which reveals a potential new avenue for leukaemia treatment.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"20 12","pages":"699-700"},"PeriodicalIF":31.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275260","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 : 2024-09-20DOI: 10.1038/s41574-024-01042-3
Bandy Chen, Stephanie Lenck, Jean-Leon Thomas, Marc Schneeberger
Exploring the glymphatic system across neurological and metabolic diseases might help us to better define the link between obesity and neurological disorders. Recent studies have identified metabolic dysfunction as a risk factor for cognitive decline and neurological disorders through disruption of the glymphatic system.
{"title":"The glymphatic system as a nexus between obesity and neurological diseases","authors":"Bandy Chen, Stephanie Lenck, Jean-Leon Thomas, Marc Schneeberger","doi":"10.1038/s41574-024-01042-3","DOIUrl":"10.1038/s41574-024-01042-3","url":null,"abstract":"Exploring the glymphatic system across neurological and metabolic diseases might help us to better define the link between obesity and neurological disorders. Recent studies have identified metabolic dysfunction as a risk factor for cognitive decline and neurological disorders through disruption of the glymphatic system.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"21 1","pages":"1-2"},"PeriodicalIF":31.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275252","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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