Pub Date : 2026-01-05DOI: 10.1038/s41574-025-01221-w
Sabrina Wangler,Marc N Jarczok,Matthew Ennis,Benedict Herhaus,Róbert Wagner,Ratika Sehgal,Martin Heni
The autonomic nervous system is a crucial mediator between the central nervous system and peripheral tissues and is essential for maintaining homeostasis. In this Review, we discuss the bidirectional communication between the autonomic nervous system and metabolic tissues in humans, focusing on the coordination of systemic glucose and lipid metabolism through autonomic signalling across changing physiological states. We also discuss the crosstalk between autonomic and immune pathways and its relevance for metabolic control. An overview of current methodologies to assess autonomic function in humans shows that quantifying organ-specific autonomic outflows remains challenging. Chronic disturbances in autonomic regulation are increasingly recognized as contributors to metabolic diseases such as obesity and type 2 diabetes mellitus. Hence, emerging therapeutic strategies targeting autonomic function could offer promising opportunities to improve metabolic health. Progress will depend on the development of tools to selectively assess autonomic input to individual metabolic organs. Addressing high inter-individual variability and capturing the temporal dynamics of organ-specific autonomic regulation will be essential for advancing mechanistic insights, ultimately enabling clinical translation.
{"title":"The autonomic nervous system in the regulation of glucose and lipid metabolism.","authors":"Sabrina Wangler,Marc N Jarczok,Matthew Ennis,Benedict Herhaus,Róbert Wagner,Ratika Sehgal,Martin Heni","doi":"10.1038/s41574-025-01221-w","DOIUrl":"https://doi.org/10.1038/s41574-025-01221-w","url":null,"abstract":"The autonomic nervous system is a crucial mediator between the central nervous system and peripheral tissues and is essential for maintaining homeostasis. In this Review, we discuss the bidirectional communication between the autonomic nervous system and metabolic tissues in humans, focusing on the coordination of systemic glucose and lipid metabolism through autonomic signalling across changing physiological states. We also discuss the crosstalk between autonomic and immune pathways and its relevance for metabolic control. An overview of current methodologies to assess autonomic function in humans shows that quantifying organ-specific autonomic outflows remains challenging. Chronic disturbances in autonomic regulation are increasingly recognized as contributors to metabolic diseases such as obesity and type 2 diabetes mellitus. Hence, emerging therapeutic strategies targeting autonomic function could offer promising opportunities to improve metabolic health. Progress will depend on the development of tools to selectively assess autonomic input to individual metabolic organs. Addressing high inter-individual variability and capturing the temporal dynamics of organ-specific autonomic regulation will be essential for advancing mechanistic insights, ultimately enabling clinical translation.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"4 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145897510","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 : 2025-12-17DOI: 10.1038/s41574-025-01227-4
Olivia Tysoe
{"title":"Exposure to fat odour during development predisposes offspring to obesity","authors":"Olivia Tysoe","doi":"10.1038/s41574-025-01227-4","DOIUrl":"10.1038/s41574-025-01227-4","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 2","pages":"65-65"},"PeriodicalIF":40.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770753","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 : 2025-12-16DOI: 10.1038/s41574-025-01224-7
João Manoel Alves
{"title":"Two roads to thermogenesis: vascular and parenchymal sympathetic innervation of brown adipose tissue.","authors":"João Manoel Alves","doi":"10.1038/s41574-025-01224-7","DOIUrl":"https://doi.org/10.1038/s41574-025-01224-7","url":null,"abstract":"","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"370 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765484","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 : 2025-12-16DOI: 10.1038/s41574-025-01225-6
Benjamin E. Clayton, David A. Guertin
Brown adipose tissue is a heat-generating organ and promising therapeutic target for treating obesity and metabolic diseases. Its presence in adults supports metabolic health, whereas its decline with age and weight gain might promote chronic disease. Efforts to understand its fascinating biology and translational potential continue to gain momentum.
{"title":"Brown adipose tissue remains hot","authors":"Benjamin E. Clayton, David A. Guertin","doi":"10.1038/s41574-025-01225-6","DOIUrl":"10.1038/s41574-025-01225-6","url":null,"abstract":"Brown adipose tissue is a heat-generating organ and promising therapeutic target for treating obesity and metabolic diseases. Its presence in adults supports metabolic health, whereas its decline with age and weight gain might promote chronic disease. Efforts to understand its fascinating biology and translational potential continue to gain momentum.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 2","pages":"72-73"},"PeriodicalIF":40.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768615","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 : 2025-12-12DOI: 10.1038/s41574-025-01219-4
Timo D. Müller
The efficacy of anti-obesity drugs that use glucagon-like peptide 1 receptor agonism and glucose-dependent insulinotropic polypeptide agonism raises critical questions about how next-generation drugs might offer increased metabolic benefits. In 2025, new research into incretin-based treatments has brought us closer to answering these questions.
{"title":"Advances in incretin-based drug discovery in 2025","authors":"Timo D. Müller","doi":"10.1038/s41574-025-01219-4","DOIUrl":"10.1038/s41574-025-01219-4","url":null,"abstract":"The efficacy of anti-obesity drugs that use glucagon-like peptide 1 receptor agonism and glucose-dependent insulinotropic polypeptide agonism raises critical questions about how next-generation drugs might offer increased metabolic benefits. In 2025, new research into incretin-based treatments has brought us closer to answering these questions.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 2","pages":"68-69"},"PeriodicalIF":40.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732748","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 : 2025-12-11DOI: 10.1038/s41574-025-01222-9
Paloma Alonso-Magdalena
The quest to understand the adverse health outcomes linked to endocrine-disrupting chemicals continued in 2025. Insights have been gained regarding their effects on metabolic health, their key characteristics, the mechanisms underlying their effects and the burden of disorders associated with exposure to these chemicals in terms of mortality and life-years lost.
{"title":"The hidden health effects of endocrine-disrupting chemicals","authors":"Paloma Alonso-Magdalena","doi":"10.1038/s41574-025-01222-9","DOIUrl":"10.1038/s41574-025-01222-9","url":null,"abstract":"The quest to understand the adverse health outcomes linked to endocrine-disrupting chemicals continued in 2025. Insights have been gained regarding their effects on metabolic health, their key characteristics, the mechanisms underlying their effects and the burden of disorders associated with exposure to these chemicals in terms of mortality and life-years lost.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 2","pages":"70-71"},"PeriodicalIF":40.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145728541","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 : 2025-12-05DOI: 10.1038/s41574-025-01218-5
Mathilde Touvier
Growing evidence has linked ultra-processed food consumption to chronic disease risk. In 2025, this field reached a turning point, with experimental, clinical and epidemiological studies converging to elucidate the underlying mechanisms at play.
{"title":"Health effects of ultra-processed food: uncovering causal mechanisms","authors":"Mathilde Touvier","doi":"10.1038/s41574-025-01218-5","DOIUrl":"10.1038/s41574-025-01218-5","url":null,"abstract":"Growing evidence has linked ultra-processed food consumption to chronic disease risk. In 2025, this field reached a turning point, with experimental, clinical and epidemiological studies converging to elucidate the underlying mechanisms at play.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"22 2","pages":"66-67"},"PeriodicalIF":40.0,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680157","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 : 2025-12-02DOI: 10.1038/s41574-025-01208-7
Maiko Sho,Rehana Qureshi,Joyce Slingerland
Many diseases, including breast cancer, increase in women after menopause and with obesity. This Review addresses novel insights that link obesity, oestrogens, inflammation and breast cancer. Adipose tissue is chronically inflamed in obesity owing to pre-adipocyte expansion and activation of nuclear factor-κB (NF-κB), which upregulate pro-inflammatory cytokines. Obesity also impairs immunosurveillance. Emerging data indicate that the major oestrogens before and after menopause have opposing effects on inflammation. In contrast to the anti-inflammatory properties of premenopausal 17β-oestradiol, the dominant postmenopausal oestrogen, oestrone, is pro-inflammatory. Oestrone is synthesized in adipocytes, therefore the expanded adipose tissue biomass in obesity increases oestrone levels in both men and women, promoting NF-κB-driven inflammation. These pro-inflammatory effects of oestrone are also oncogenic, promoting breast cancer progression in laboratory models. The dominance of oestrone and loss of 17β-oestradiol might underlie the increased prevalence of hormone-responsive breast cancer after menopause, particularly in the context of obesity. Although oestrogens account for much of the excess breast cancer risk with obesity, data on 17β-oestradiol and oestrone levels in the breast and circulation in postmenopausal women, whether or not obesity is present, are limited. Weight loss is associated with reduced breast cancer risk and improved outcomes. The opportunity to use potent weight loss drugs as adjuncts to cancer therapy is discussed.
{"title":"Oestrogen changes at menopause: insights into obesity-associated breast risk and outcomes.","authors":"Maiko Sho,Rehana Qureshi,Joyce Slingerland","doi":"10.1038/s41574-025-01208-7","DOIUrl":"https://doi.org/10.1038/s41574-025-01208-7","url":null,"abstract":"Many diseases, including breast cancer, increase in women after menopause and with obesity. This Review addresses novel insights that link obesity, oestrogens, inflammation and breast cancer. Adipose tissue is chronically inflamed in obesity owing to pre-adipocyte expansion and activation of nuclear factor-κB (NF-κB), which upregulate pro-inflammatory cytokines. Obesity also impairs immunosurveillance. Emerging data indicate that the major oestrogens before and after menopause have opposing effects on inflammation. In contrast to the anti-inflammatory properties of premenopausal 17β-oestradiol, the dominant postmenopausal oestrogen, oestrone, is pro-inflammatory. Oestrone is synthesized in adipocytes, therefore the expanded adipose tissue biomass in obesity increases oestrone levels in both men and women, promoting NF-κB-driven inflammation. These pro-inflammatory effects of oestrone are also oncogenic, promoting breast cancer progression in laboratory models. The dominance of oestrone and loss of 17β-oestradiol might underlie the increased prevalence of hormone-responsive breast cancer after menopause, particularly in the context of obesity. Although oestrogens account for much of the excess breast cancer risk with obesity, data on 17β-oestradiol and oestrone levels in the breast and circulation in postmenopausal women, whether or not obesity is present, are limited. Weight loss is associated with reduced breast cancer risk and improved outcomes. The opportunity to use potent weight loss drugs as adjuncts to cancer therapy is discussed.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"119 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145657081","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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