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A trio of trials on hormone receptor agonists for MASLD 对治疗 MASLD 的激素受体激动剂进行了三项试验。
IF 31 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-07-01 DOI: 10.1038/s41574-024-01015-6
Shimona Starling
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引用次数: 0
Metabolically healthy obesity: from epidemiology and mechanisms to clinical implications 代谢健康的肥胖症:从流行病学和机制到临床意义
IF 40.5 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-27 DOI: 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.

代谢健康的概念,尤其是肥胖症的代谢健康概念,已经引起了科学界的广泛关注,并越来越多地被用于确定心血管疾病和糖尿病相关并发症的风险。本综述评估了目前对代谢健康肥胖(MHO)的理解。首先,我们介绍了这一概念的历史演变。其次,我们讨论了支持和反对 MHO 存在的证据、多年来 MHO 不同定义的使用情况以及为提供 MHO 新定义所做的努力。第三,我们强调了有关 MHO 心血管风险的流行病学数据,与代谢健康的正常体重个体相比,使用广泛使用的 MHO 定义,估计 MHO 的心血管风险中度升高,但使用新的 MHO 定义,则可能不会升高。第四,我们将讨论有关 MHO 所涉及的生理机制的新发现,以及这些知识如何帮助识别和描述 MHO 患者和代谢不健康的正常体重者。最后,我们将讨论如何在临床实践中将 MHO 概念用于风险分层和治疗。
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引用次数: 0
Progestin production by the gut microbiota 肠道微生物群产生孕激素
IF 31 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-26 DOI: 10.1038/s41574-024-01013-8
Claire Greenhill
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引用次数: 0
The relationship between the gut microbiota and thyroid disorders 肠道微生物群与甲状腺疾病的关系
IF 31 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-21 DOI: 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.
甲状腺疾病很常见,女性发病率高于男性,病变范围从炎症性到肿瘤性不等。自身免疫性甲状腺疾病(AITD)影响着2-5%的人口,而甲状腺癌则是最常见的内分泌恶性肿瘤。对自身免疫性甲状腺疾病的治疗仍局限于控制而非预防或治愈。在确定易患 AITD 和甲状腺癌的基因变异方面已经取得了进展,但所有甲状腺疾病发病率的不断上升表明,除基因外,还有其他因素参与其中。肠道微生物群在出生前就开始发育,对饮食和环境高度敏感,为非传染性疾病变成传染性疾病提供了潜在机制。它的功能不仅限于维持肠道完整性:肠道微生物群还能调节免疫系统,促进甲状腺激素代谢,并能产生或分解致癌物质,所有这些都与 AITD 和甲状腺癌有关。在动物模型中进行的观察性和干预性研究支持肠道微生物群在 AITD 中的作用,人类队列中的一些报告也证实了这一点,尽管地域差异明显。关于微生物群在甲状腺癌中的作用的报告则较为有限,但有证据支持肠道菌群失调与甲状腺癌之间存在关系。
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引用次数: 0
Mind the (human-based new approach methodology) gap! 注意(以人为本的新方法论)差距!
IF 31 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-19 DOI: 10.1038/s41574-024-01011-w
Denise D. Belsham
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引用次数: 0
Debunking the myths of intermittent fasting 揭开间歇性禁食的神秘面纱
IF 31 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-19 DOI: 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.
尽管越来越多的证据支持使用间歇性断食作为一种安全有效的减肥干预措施,但在大众文化中仍然存在许多关于断食的神话。在此,我们将回顾一些没有科学证据支持的关于间歇性禁食的常见观念。
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引用次数: 0
The relationship between SARS-CoV-2 infection and type 1 diabetes mellitus SARS-CoV-2 感染与 1 型糖尿病之间的关系
IF 31 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-18 DOI: 10.1038/s41574-024-01004-9
Cyril Debuysschere, Magloire Pandoua Nekoua, Enagnon Kazali Alidjinou, Didier Hober
Environmental factors, in particular viral infections, are thought to have an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The COVID-19 pandemic reinforced this hypothesis as many observational studies and meta-analyses reported a notable increase in the incidence of T1DM following infection with SARS-CoV-2 as well as an association between SARS-CoV-2 infection and the risk of new-onset T1DM. Experimental evidence suggests that human β-cells express SARS-CoV-2 receptors and that SARS-CoV-2 can infect and replicate in β-cells, resulting in structural or functional alterations of these cells. These alterations include reduced numbers of insulin-secreting granules, impaired pro-insulin (or insulin) secretion, and β-cell transdifferentiation or dedifferentiation. The inflammatory environment induced by local or systemic SARS-CoV-2 infection might result in a set of signals (such as pro-inflammatory cytokines) that lead to β-cell alteration or apoptosis or to a bystander activation of T cells and disruption of peripheral tolerance that triggers autoimmunity. Other mechanisms, such as viral persistence, molecular mimicry and activation of endogenous human retroviruses, are also likely to be involved in the pathogenesis of T1DM following SARS-CoV-2 infection. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies. Many studies identified an increase in the incidence of type 1 diabetes mellitus (T1DM) during the COVID-19 pandemic, but other reports do not support this association. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies.
环境因素,尤其是病毒感染,被认为在 1 型糖尿病(T1DM)的发病机制中起着重要作用。COVID-19 大流行强化了这一假设,因为许多观察性研究和荟萃分析报告称,感染 SARS-CoV-2 后,T1DM 的发病率明显增加,而且 SARS-CoV-2 感染与新发 T1DM 的风险之间存在关联。实验证据表明,人的β细胞表达SARS-CoV-2受体,SARS-CoV-2可感染β细胞并在其中复制,导致这些细胞的结构或功能发生改变。这些改变包括胰岛素分泌颗粒数量减少、促胰岛素(或胰岛素)分泌受损、β 细胞发生转分化或去分化。局部或全身感染 SARS-CoV-2 后诱发的炎症环境可能会产生一系列信号(如促炎细胞因子),导致 β 细胞改变或凋亡,或导致 T 细胞的旁观者激活和外周耐受性破坏,从而引发自身免疫。其他机制,如病毒持续存在、分子模仿和激活内源性人类逆转录病毒,也可能参与了 SARS-CoV-2 感染后 T1DM 的发病机制。本综述利用流行病学、临床和实验研究的证据,探讨了 SARS-CoV-2 感染参与 T1DM 发病的问题。
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引用次数: 0
Circulating non-coding RNA biomarkers of endocrine tumours 内分泌肿瘤的循环非编码 RNA 生物标记物
IF 31 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-17 DOI: 10.1038/s41574-024-01005-8
Henriett Butz, Attila Patócs, Peter Igaz
Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background. No preoperative biomarkers of malignancy are available for several forms of these endocrine tumours. Moreover, biomarkers are also needed for the follow-up of tumour progression (especially in hormonally inactive tumours), prognosis and treatment efficacy monitoring. Circulating blood-borne ncRNAs show promising utility as biomarkers. These ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, are involved in several aspects of gene expression regulation, and their stability and tissue-specific expression could make them ideal biomarkers. However, no circulating ncRNA biomarkers have yet been introduced into routine clinical practice, which is mostly owing to methodological and standardization problems. In this Review, following a brief synopsis of these endocrine tumours and the biology of ncRNAs, the major research findings, pathomechanisms and methodological questions are discussed along with an outlook for future studies. Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. This Review outlines ncRNA biology, before discussing research findings on ncRNAs in endocrine tumours and their potential utility as biomarkers, ending with an outlook for future studies.
循环非编码 RNA(ncRNA)分子正被研究作为多种肿瘤(包括垂体、甲状旁腺、胰腺和肾上腺的内分泌肿瘤)的恶性程度、预后和随访的生物标志物。这些肿瘤大多被归类为神经内分泌肿瘤(包括神经内分泌肿瘤和神经内分泌癌),包括侵袭性不同的肿瘤。由于其临床表现、病理机制和遗传背景相似,我们在本综述中将它们放在一起讨论。目前还没有针对几种内分泌肿瘤的术前恶性生物标志物。此外,还需要生物标志物来跟踪肿瘤的进展(尤其是激素不活跃的肿瘤)、预后和疗效监测。循环血液中的 ncRNA 显示出作为生物标记物的巨大潜力。这些 ncRNA(包括 microRNA、长非编码 RNA 和环状 RNA)参与基因表达调控的多个方面,其稳定性和组织特异性表达使其成为理想的生物标记物。然而,目前还没有循环 ncRNA 生物标志物被引入常规临床实践,这主要是由于方法学和标准化方面的问题。本综述简要概述了这些内分泌肿瘤和 ncRNAs 的生物学特性,讨论了主要研究成果、病理机制和方法学问题,并对未来研究进行了展望。
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引用次数: 0
Evidence for somatic mutation screening on aggressive prolactinomas 对侵袭性催乳素瘤进行体细胞突变筛查的证据
IF 31 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-17 DOI: 10.1038/s41574-024-01010-x
Marily Theodoropoulou, Stephan Petersenn, Philippe Chanson, Gerald Raverot
The recent Consensus Statement on the diagnosis and management of prolactin-secreting pituitary adenomas (prolactinomas) drew attention to molecular pathogenetic mechanisms. We comment that somatic screening for SF3B1 hotspot variants in select cases might alert to aggressive tumour behaviour and prompt the timely management and intense follow up of these challenging tumours.
最近关于分泌催乳素的垂体腺瘤(催乳素瘤)的诊断和管理的共识声明引起了人们对分子致病机制的关注。我们认为,对部分病例进行体细胞SF3B1热点变异筛查,可能会对侵袭性肿瘤行为发出警报,并促使对这些具有挑战性的肿瘤进行及时处理和密切随访。
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引用次数: 0
Gut hormones and bone homeostasis: potential therapeutic implications 肠道激素与骨平衡:潜在的治疗意义。
IF 31 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-06-10 DOI: 10.1038/s41574-024-01000-z
Béatrice Bouvard, Guillaume Mabilleau
Bone resorption follows a circadian rhythm, with a marked reduction in circulating markers of resorption (such as carboxy-terminal telopeptide region of collagen type I in serum) in the postprandial period. Several gut hormones, including glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1) and GLP2, have been linked to this effect in humans and rodent models. These hormones are secreted from enteroendocrine cells in the gastrointestinal tract in response to a variety of stimuli and effect a wide range of physiological processes within and outside the gut. Single GLP1, dual GLP1–GIP or GLP1–glucagon and triple GLP1–GIP–glucagon receptor agonists have been developed for the treatment of type 2 diabetes mellitus and obesity. In addition, single GIP, GLP1 and GLP2 analogues have been investigated in preclinical studies as novel therapeutics to improve bone strength in bone fragility disorders. Dual GIP–GLP2 analogues have been developed that show therapeutic promise for bone fragility in preclinical studies and seem to exert considerable activity at the bone material level. This Review summarizes the evidence of the action of gut hormones on bone homeostasis and physiology. This Review summarizes the evidence regarding the actions of gut hormones on bone homeostasis and physiology. The potential implications for the development of future therapeutics to treat bone fragility are considered.
骨吸收遵循昼夜节律,餐后循环中的骨吸收标志物(如血清中 I 型胶原蛋白的羧基端端肽区域)明显减少。在人类和啮齿动物模型中,几种肠道激素,包括葡萄糖依赖性促胰岛素多肽(GIP)、胰高血糖素样肽 1(GLP1)和 GLP2,都与这种效应有关。这些激素由胃肠道中的肠内分泌细胞分泌,对各种刺激做出反应,并影响肠道内外的各种生理过程。目前已开发出单一 GLP1、双 GLP1-GIP 或 GLP1-Glucagon 以及三重 GLP1-GIP-Glucagon 受体激动剂,用于治疗 2 型糖尿病和肥胖症。此外,单一 GIP、GLP1 和 GLP2 类似物已作为新型疗法在临床前研究中进行了调查,以改善骨质脆弱症患者的骨强度。目前已开发出双 GIP-GLP2 类似物,它们在临床前研究中显示出治疗骨脆性的前景,并且似乎在骨材料层面发挥了相当大的活性。本综述总结了肠道激素对骨稳态和生理学作用的证据。
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引用次数: 0
期刊
Nature Reviews Endocrinology
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