Premature ovarian insufficiency (POI) is a highly heterogeneous reproductive disorder in both its etiology and clinical presentation. The epidemiological characteristics of POI suggest that its occurrence likely involves a combination of genetic and environmental factors. Deciphering the pathogenic mechanisms of POI is crucial for improving reproductive outcomes as well as managing the long-term complications associated with ovarian dysfunction. Recent studies expand the list of POI causal genes and promote the viability of genetic diagnosis. However, whole exome sequencing studies in large-scale POI cohorts and genome-wide association studies on the age at natural menopause have uncovered a complex genetic architecture underlying POI that includes monogenic and oligogenic inheritance modes, emphasizing the difficulties in genetic diagnosis, especially for the isolated cases. Moreover, our understanding of the physiology of ovarian aging has greatly benefited from recent advances in multiomics analysis, expanding our perspective on the pathogenic mechanisms and potential targeted therapeutic strategies for POI. In this review, we summarize the epidemiological characteristics of POI, as well as progress in genetic and epigenetic etiologies, and discuss advances in pharmacology and material science that will likely contribute to new interventions for ovarian aging. Finally, this review offers new insights into prospects for early diagnosis and treatment of POI, while identifying persistent challenges and potential solutions to be addressed through future research.
{"title":"Epidemiology, Genetic Etiology, and Intervention of Premature Ovarian Insufficiency.","authors":"Ting Guo, Hongyuan Liu, Bingying Xu, Yu Qi, Keyan Xu, Xinyi Wu, Xinmiao He, Yingying Qin, Zi-Jiang Chen","doi":"10.1210/endrev/bnaf011","DOIUrl":"10.1210/endrev/bnaf011","url":null,"abstract":"<p><p>Premature ovarian insufficiency (POI) is a highly heterogeneous reproductive disorder in both its etiology and clinical presentation. The epidemiological characteristics of POI suggest that its occurrence likely involves a combination of genetic and environmental factors. Deciphering the pathogenic mechanisms of POI is crucial for improving reproductive outcomes as well as managing the long-term complications associated with ovarian dysfunction. Recent studies expand the list of POI causal genes and promote the viability of genetic diagnosis. However, whole exome sequencing studies in large-scale POI cohorts and genome-wide association studies on the age at natural menopause have uncovered a complex genetic architecture underlying POI that includes monogenic and oligogenic inheritance modes, emphasizing the difficulties in genetic diagnosis, especially for the isolated cases. Moreover, our understanding of the physiology of ovarian aging has greatly benefited from recent advances in multiomics analysis, expanding our perspective on the pathogenic mechanisms and potential targeted therapeutic strategies for POI. In this review, we summarize the epidemiological characteristics of POI, as well as progress in genetic and epigenetic etiologies, and discuss advances in pharmacology and material science that will likely contribute to new interventions for ovarian aging. Finally, this review offers new insights into prospects for early diagnosis and treatment of POI, while identifying persistent challenges and potential solutions to be addressed through future research.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"621-651"},"PeriodicalIF":22.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771731","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}
Experimental animal and human studies illustrate the effect of various stress forms on the thyroid gland and the regulation of thyroid hormones (THs) through the thyrotropic multiloop control circuit. The hypothalamic-pituitary-thyroid axis (HPT) axis is part of the physiological stress system and mediates key regulators of metabolic activity during stress response. Genetically characterized individuals are more affected in their response to stressors, and their psychological response is extremely amplified. This leads to significant increases in TH serum levels as soon as a negative stressor appears. Physical stressors are used to induce psychological stress (eg, physical exercise, starvation, sleep deprivation, hypoxia, and cold temperatures), all of which impact thyroid function. In addition, somatic illnesses may also affect the thyroid gland or may be related to a thyroidal dysfunction. As a psychosocial stressor in animal models, neonatal separation from the mother was used, affecting energy homeostasis and causing an increase in thyroliberin (TRH) expression in female rats and an increase in TRH degrading ectoenzyme in male rats. In mice with restrained stress, THs are important mediators of accelerated tumor growth. In human studies, isolated sexual abuse in childhood doubles the risk of thyroid dysfunction, with puerperal depression after sexual abuse in childhood increasing the risk for HPT axis disorders and elevated thyroid autoantibodies 4-fold. In addition, psychological illnesses influence thyroid function. In the future, laboratory studies with standardized induction of various stress forms are warranted to better understand stress-induced effects on the HPT axis and their corresponding mechanisms.
{"title":"Stress and Thyroid Function-From Bench to Bedside.","authors":"Katja Petrowski, George J Kahaly","doi":"10.1210/endrev/bnaf015","DOIUrl":"10.1210/endrev/bnaf015","url":null,"abstract":"<p><p>Experimental animal and human studies illustrate the effect of various stress forms on the thyroid gland and the regulation of thyroid hormones (THs) through the thyrotropic multiloop control circuit. The hypothalamic-pituitary-thyroid axis (HPT) axis is part of the physiological stress system and mediates key regulators of metabolic activity during stress response. Genetically characterized individuals are more affected in their response to stressors, and their psychological response is extremely amplified. This leads to significant increases in TH serum levels as soon as a negative stressor appears. Physical stressors are used to induce psychological stress (eg, physical exercise, starvation, sleep deprivation, hypoxia, and cold temperatures), all of which impact thyroid function. In addition, somatic illnesses may also affect the thyroid gland or may be related to a thyroidal dysfunction. As a psychosocial stressor in animal models, neonatal separation from the mother was used, affecting energy homeostasis and causing an increase in thyroliberin (TRH) expression in female rats and an increase in TRH degrading ectoenzyme in male rats. In mice with restrained stress, THs are important mediators of accelerated tumor growth. In human studies, isolated sexual abuse in childhood doubles the risk of thyroid dysfunction, with puerperal depression after sexual abuse in childhood increasing the risk for HPT axis disorders and elevated thyroid autoantibodies 4-fold. In addition, psychological illnesses influence thyroid function. In the future, laboratory studies with standardized induction of various stress forms are warranted to better understand stress-induced effects on the HPT axis and their corresponding mechanisms.</p>","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":" ","pages":"709-735"},"PeriodicalIF":22.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309717","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}
S R Murthy Madiraju,Elite Possik,Fahd Al-Mulla,Christopher J Nolan,Marc Prentki
Glycerol and glycerol-3-phosphate are key metabolites at the intersection of carbohydrate, lipid and energy metabolism. Their production and usage are organismal and cell type specific. Glycerol has unique physicochemical properties enabling it to function as an osmolyte, protein structure stabilizer, antimicrobial and antifreeze agent, important to preservation of many biological functions. Glycerol and glycerol-3-phosphate are implicated in many physiological and disease processes relating to energy metabolism, thermoregulation, hydration, skin health, male fertility, aging, and cancer. Glycerol has countless applications in the food, pharmaceutical and cosmetics industries. It is used as a sweetener, preservative, thickening agent, humectant, osmolyte and cryoprotectant. It is widely used in skin and wound care products, laxatives, in cell and tissue preservation and in medicines for numerous conditions. Here, we review the multiple uses and functions of glycerol and glycerol-3-phosphate and associated transporters, enzymes and target genes in health, senescence and disease. We discuss the evidence that glycerol may be present at much higher levels in tissues and cells than in the blood. We bring particular focus to the newly identified glycerol shunt in the direct formation of glycerol independent of lipolysis and as a pathway allowing cells to adapt to various stresses. Relevant to chronic metabolic diseases, cancer and aging, glycerol and glycerol-3-phosphate presents important translational implications and thus warrants much more attention.
{"title":"Glycerol and glycerol-3-phosphate: multifaceted metabolites in metabolism, cancer and other diseases.","authors":"S R Murthy Madiraju,Elite Possik,Fahd Al-Mulla,Christopher J Nolan,Marc Prentki","doi":"10.1210/endrev/bnaf033","DOIUrl":"https://doi.org/10.1210/endrev/bnaf033","url":null,"abstract":"Glycerol and glycerol-3-phosphate are key metabolites at the intersection of carbohydrate, lipid and energy metabolism. Their production and usage are organismal and cell type specific. Glycerol has unique physicochemical properties enabling it to function as an osmolyte, protein structure stabilizer, antimicrobial and antifreeze agent, important to preservation of many biological functions. Glycerol and glycerol-3-phosphate are implicated in many physiological and disease processes relating to energy metabolism, thermoregulation, hydration, skin health, male fertility, aging, and cancer. Glycerol has countless applications in the food, pharmaceutical and cosmetics industries. It is used as a sweetener, preservative, thickening agent, humectant, osmolyte and cryoprotectant. It is widely used in skin and wound care products, laxatives, in cell and tissue preservation and in medicines for numerous conditions. Here, we review the multiple uses and functions of glycerol and glycerol-3-phosphate and associated transporters, enzymes and target genes in health, senescence and disease. We discuss the evidence that glycerol may be present at much higher levels in tissues and cells than in the blood. We bring particular focus to the newly identified glycerol shunt in the direct formation of glycerol independent of lipolysis and as a pathway allowing cells to adapt to various stresses. Relevant to chronic metabolic diseases, cancer and aging, glycerol and glycerol-3-phosphate presents important translational implications and thus warrants much more attention.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"24 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025375","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":"Correction to: \"Glucose-Dependent Insulinotropic Polypeptide in Incretin Physiology: Role in Health and Disease\".","authors":"","doi":"10.1210/endrev/bnaf028","DOIUrl":"https://doi.org/10.1210/endrev/bnaf028","url":null,"abstract":"","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"38 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930171","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":"Correction to: \"The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives\".","authors":"","doi":"10.1210/endrev/bnaf024","DOIUrl":"https://doi.org/10.1210/endrev/bnaf024","url":null,"abstract":"","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"185 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825466","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":"Correction to: \"Imaging of Pheochromocytomas and Paragangliomas\".","authors":"","doi":"10.1210/endrev/bnaf023","DOIUrl":"https://doi.org/10.1210/endrev/bnaf023","url":null,"abstract":"","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"143 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825471","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}
The multiple physiological effects of gut hormones in different metabolic tissues make them attractive therapeutic targets for the treatment of metabolic diseases. Currently, only GLP-1 receptor-based agonists and oral DPP-4 inhibitors are available on the market. Despite their positive clinical outcomes across a range of indications these treatments present several clinical challenges, including high costs, the need for peptide injections, and requirements for repeated administration. These limitations have driven research into improved GLP-1-based therapies, such as oral small-molecule agonists and novel drug delivery strategies based on emerging GLP-1 medicines. This article describes the challenges in clinical application and development of GLP-1-based pharmacotherapies. We review the development of oral small-molecule agonists and various drug delivery technologies, including ultralong-acting injectable technologies, continuous-acting implantable pumps, smart-acting electronic devices, nutrient-induced cell therapies, and noninvasive delivery systems. We discuss the current state of research, challenges to overcome, and opportunities to improve patient compliance and clinical outcomes. Additionally, we explore how endocrinological effects and patient-oriented needs can guide the development of advanced GLP-1 medicines.
{"title":"Innovative molecules and delivery technologies enabling the future of GLP-1-based therapies.","authors":"Yining Xu,Daniel J Drucker,Giovanni Traverso,Ana Beloqui","doi":"10.1210/endrev/bnaf027","DOIUrl":"https://doi.org/10.1210/endrev/bnaf027","url":null,"abstract":"The multiple physiological effects of gut hormones in different metabolic tissues make them attractive therapeutic targets for the treatment of metabolic diseases. Currently, only GLP-1 receptor-based agonists and oral DPP-4 inhibitors are available on the market. Despite their positive clinical outcomes across a range of indications these treatments present several clinical challenges, including high costs, the need for peptide injections, and requirements for repeated administration. These limitations have driven research into improved GLP-1-based therapies, such as oral small-molecule agonists and novel drug delivery strategies based on emerging GLP-1 medicines. This article describes the challenges in clinical application and development of GLP-1-based pharmacotherapies. We review the development of oral small-molecule agonists and various drug delivery technologies, including ultralong-acting injectable technologies, continuous-acting implantable pumps, smart-acting electronic devices, nutrient-induced cell therapies, and noninvasive delivery systems. We discuss the current state of research, challenges to overcome, and opportunities to improve patient compliance and clinical outcomes. Additionally, we explore how endocrinological effects and patient-oriented needs can guide the development of advanced GLP-1 medicines.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"77 6 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769588","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}
The hypothalamus is the key regulator of the human energy's balance. Hypothalamic dysfunction leads to (morbid) hypothalamic obesity, but may have many more consequences such as hypopituitarism, adipsia, disruption of the circadian rhythm, decreased energy expenditure, low core body temperature and behavioral changes. Many patients with hypothalamic dysfunction experience chronic fatigue, increased daytime sleepiness, headaches, inactivity and mood disorders which all in its turn itself may contribute to the development of obesity. Adipsic AVP-deficiency, severe hypothermia, uncontrollable hyperphagia and severe mood disorders may require 24/7 management. Signs and symptoms may be severe or mild. Severe hypothalamic dysfunction is usually readily diagnosed, but less severe hypothalamic dysfunction is much harder to recognize, because, among other things, of its multifaceted presentation. Through raising awareness and by better categorization of the different clinical signs and symptoms of hypothalamic dysfunction within different domains, the underlying cause for fatigue and obesity observed in patients with hypothalamic dysfunction may be better understood, which in its turn, will open new perspectives on successful management options. In this review, the state of the art for diagnostics and management of acquired hypothalamic dysfunction is summarized and a new management algorithm is suggested. The lessons learned from pediatric patients with acquired hypothalamic dysfunction, including hypothalamic obesity management through the different clinical domains, may also prove to be useful for patients with congenital or genetic forms of hypothalamic dysfunction resulting in fatigue and obesity, as well as for children with presumed "common" obesity.
{"title":"Management of Acquired Hypothalamic Dysfunction and the Hypothalamic Syndrome; it is more than obesity.","authors":"Hanneke M van Santen,Hermann L Müller","doi":"10.1210/endrev/bnaf025","DOIUrl":"https://doi.org/10.1210/endrev/bnaf025","url":null,"abstract":"The hypothalamus is the key regulator of the human energy's balance. Hypothalamic dysfunction leads to (morbid) hypothalamic obesity, but may have many more consequences such as hypopituitarism, adipsia, disruption of the circadian rhythm, decreased energy expenditure, low core body temperature and behavioral changes. Many patients with hypothalamic dysfunction experience chronic fatigue, increased daytime sleepiness, headaches, inactivity and mood disorders which all in its turn itself may contribute to the development of obesity. Adipsic AVP-deficiency, severe hypothermia, uncontrollable hyperphagia and severe mood disorders may require 24/7 management. Signs and symptoms may be severe or mild. Severe hypothalamic dysfunction is usually readily diagnosed, but less severe hypothalamic dysfunction is much harder to recognize, because, among other things, of its multifaceted presentation. Through raising awareness and by better categorization of the different clinical signs and symptoms of hypothalamic dysfunction within different domains, the underlying cause for fatigue and obesity observed in patients with hypothalamic dysfunction may be better understood, which in its turn, will open new perspectives on successful management options. In this review, the state of the art for diagnostics and management of acquired hypothalamic dysfunction is summarized and a new management algorithm is suggested. The lessons learned from pediatric patients with acquired hypothalamic dysfunction, including hypothalamic obesity management through the different clinical domains, may also prove to be useful for patients with congenital or genetic forms of hypothalamic dysfunction resulting in fatigue and obesity, as well as for children with presumed \"common\" obesity.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"56 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756186","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}
The growth hormone (GH)-insulin-like growth factor-I (IGF-I) endocrine system has a central role in metabolism and growth. The Somatomedin Hypothesis, postulated in the mid-1950s, claimed that the biological activities of pituitary GH are mediated by a liver-produced peptide termed somatomedin or IGF-I. In spite of the fact that this theory has been modified several times throughout the years to accommodate new developments in the field, it is still regarded as the main conceptual framework in the area of GH and IGF-I biology. Regardless of the unifying view that emanates from the Somatomedin Hypothesis, several opposing activities of GH and IGF-I have been described over the years. The present review addresses some of these metabolic activities, including diverging effects of these hormones on serum lipoprotein(a), sex hormone binding globulin, insulin secretion and adiponectin/leptin biology. In addition, we propose a number of potential mechanisms that can probably provide a cellular and biochemical basis for these divergent actions. Understanding the complex interactions between the GH and IGF-I signaling pathways might improve our understanding of basic molecular endocrine processes and result in potential clinical applications.
{"title":"Opposing Metabolic Effects of Growth Hormone and IGF-I: Review and Clinical Implications.","authors":"Zvi Laron,Haim Werner","doi":"10.1210/endrev/bnaf022","DOIUrl":"https://doi.org/10.1210/endrev/bnaf022","url":null,"abstract":"The growth hormone (GH)-insulin-like growth factor-I (IGF-I) endocrine system has a central role in metabolism and growth. The Somatomedin Hypothesis, postulated in the mid-1950s, claimed that the biological activities of pituitary GH are mediated by a liver-produced peptide termed somatomedin or IGF-I. In spite of the fact that this theory has been modified several times throughout the years to accommodate new developments in the field, it is still regarded as the main conceptual framework in the area of GH and IGF-I biology. Regardless of the unifying view that emanates from the Somatomedin Hypothesis, several opposing activities of GH and IGF-I have been described over the years. The present review addresses some of these metabolic activities, including diverging effects of these hormones on serum lipoprotein(a), sex hormone binding globulin, insulin secretion and adiponectin/leptin biology. In addition, we propose a number of potential mechanisms that can probably provide a cellular and biochemical basis for these divergent actions. Understanding the complex interactions between the GH and IGF-I signaling pathways might improve our understanding of basic molecular endocrine processes and result in potential clinical applications.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"34 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719998","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}
The adaptive starvation response allows us to survive periods of starvation - a characteristic of the environment in which humans evolved. We are now in an evolutionary transition from a global environment which was characterized by periods of famine to a world where obesity and caloric excess have become a new reality, but the mechanisms of fasting physiology remain relevant. First, many parts of the world are still plagued by famine with insufficient food resources and therefore the adaptive mechanisms required for survival during periods of decreased caloric intake are not simply relevant to our evolutionary past. Second, the obesity epidemic provides strong rationale for understanding the biology of fasting, as the same efficiencies that have evolved to allow us to survive periods of starvation also likely drive a genetic predisposition to obesity, and therefore some of the adaptive mechanisms may be maladaptive in the setting of food excess. A third compelling reason to explore the biology of fasting is that in model organisms, caloric restriction without overt starvation, is an intervention that prolongs lifespan. The purpose of this review is to provide an overview of the biology of fasting. We will highlight potential mechanisms of benefit from fasting as well as examine data from model organisms and humans that indicate potential health risks to fasting, particularly related to bone fragility. Finally, we will review clinical studies to date that have investigated the effects of fasting on metabolic outcomes and suggest signals of benefit.
{"title":"A critical assessment of fasting to promote metabolic health and longevity.","authors":"Pouneh K Fazeli,Matthew L Steinhauser","doi":"10.1210/endrev/bnaf021","DOIUrl":"https://doi.org/10.1210/endrev/bnaf021","url":null,"abstract":"The adaptive starvation response allows us to survive periods of starvation - a characteristic of the environment in which humans evolved. We are now in an evolutionary transition from a global environment which was characterized by periods of famine to a world where obesity and caloric excess have become a new reality, but the mechanisms of fasting physiology remain relevant. First, many parts of the world are still plagued by famine with insufficient food resources and therefore the adaptive mechanisms required for survival during periods of decreased caloric intake are not simply relevant to our evolutionary past. Second, the obesity epidemic provides strong rationale for understanding the biology of fasting, as the same efficiencies that have evolved to allow us to survive periods of starvation also likely drive a genetic predisposition to obesity, and therefore some of the adaptive mechanisms may be maladaptive in the setting of food excess. A third compelling reason to explore the biology of fasting is that in model organisms, caloric restriction without overt starvation, is an intervention that prolongs lifespan. The purpose of this review is to provide an overview of the biology of fasting. We will highlight potential mechanisms of benefit from fasting as well as examine data from model organisms and humans that indicate potential health risks to fasting, particularly related to bone fragility. Finally, we will review clinical studies to date that have investigated the effects of fasting on metabolic outcomes and suggest signals of benefit.","PeriodicalId":11544,"journal":{"name":"Endocrine reviews","volume":"11 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693511","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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