English
中文大脑食欲中枢图谱有望推动研发肥胖与糖尿病新疗法
“HYPOMAP（人类下丘脑空间细胞图谱）证实了下丘脑在体重调控中的关键作用，也帮我们找到了与肥胖相关的新基因。”
——贾尔斯·叶奥
“HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesity”
——Giles Yeo
科学家绘制出了迄今为止最详细的人类下丘脑图谱。下丘脑是大脑中调控体重、食欲、睡眠和压力等多种重要生理功能的关键区域。
Scientists have created the most detailed map to date of the human hypothalamus, a crucial brain region that regulates body weight, appetite, sleep, and stress.
近日在《Nature》发表的名为HYPOMAP（人类下丘脑空间细胞图谱）的全面资源提供了前所未有的大脑食欲中枢图谱，有望加速肥胖与二型糖尿病治疗方法的研发。
Published recently in Nature, this comprehensive resource, called HYPOMAP, provides an unparalleled view of the brain’s appetite centre and promises to accelerate the development of treatments for obesity and type 2 diabetes.
下丘脑常被称为大脑的“控制中心”，控制着许多最重要的生理过程。我们对下丘脑的大部分认知来源于动物研究，尤其是小鼠模型，但如何将这些研究发现用到人类身上长期以来都是一大挑战。
The hypothalamus is often described as the brain’s ‘control centre’, orchestrating many of the body’s most vital processes. While much of our knowledge of the hypothalamus comes from animal studies, especially in mice, translating these findings to humans has long been a challenge.
HYPOMAP通过绘制人类下丘脑的单细胞图谱填补了这一研究空白。该图谱不仅标注了超过450种独特的细胞类型，还揭示了人类与小鼠下丘脑之间的关键差异——这些差异对药物研发具有重大意义。
HYPOMAP bridges this gap by providing an atlas of the individual cells within the human hypothalamus. This resource not only charts over 450 unique cell types but also highlights key differences between the human and mouse hypothalamus — differences that have major implications for drug development.
“这项研究对理解人类下丘脑而言具有变革性意义。”该论文的资深作者、剑桥大学代谢科学研究所-代谢研究实验室（IMS-MRL）及英国医学研究理事会（MRC）代谢疾病研究部的贾尔斯·叶奥教授 (Giles Yeo) 表示。
“This is a game-changer for understanding the human hypothalamus,” said Professor Giles Yeo, senior author of the study from the Institute of Metabolic Science-Metabolic Research Laboratories (IMS-MRL) and MRC Metabolic Diseases Unit, University of Cambridge.
“HYPOMAP不仅证实了下丘脑在体重调控中的关键作用，还帮我们找到了与肥胖相关的新基因。它为我们提供了一张‘路线图’，以便研发更有效且专门针对人类的治疗方案。”
“HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesity. It gives us a roadmap to develop more effective, human-specific therapies.”
和位于科隆的马克斯·普朗克代谢研究所（Max Planck Institute for Metabolism Research）研究团队一起，叶奥教授及其同事使用前沿技术对来自18位人类供体的40多万个细胞进行了分析。
Together with researchers at the Max Planck Institute for Metabolism Research in Cologne, Professor Yeo and colleagues used cutting-edge technologies to analyse over 400,000 cells from 18 human donors.
HYPOMAP使研究人员能够精准识别特定细胞类型，深入了解其基因特征，并探索其与邻近细胞的相互作用。这份精细的细胞图谱为进一步了解调控食欲与能量平衡的通路，及其他功能如睡眠和压力反应等，提供了宝贵思路。
HYPOMAP allows researchers to pinpoint specific cell types, understand their genetic profiles, and explore how they interact with neighbouring cells. This detailed cellular resolution offers invaluable insights into the circuits that regulate appetite and energy balance, as well as other functions such as sleep and stress responses.
与小鼠下丘脑图谱的对比揭示了两者之间既有相似之处，同时也存在关键差异。值得注意的是，小鼠下丘脑中的某些神经元具有GLP-1受体（GLP-1R），而GLP-1是司美格鲁肽（semaglutide）等热门减重药物的靶点，但在人类下丘脑中，这些神经元却并不存在。
Comparison with a mouse hypothalamus atlas revealed both similarities and critical differences. Notably, some neurons in the mouse hypothalamus have receptors for GLP-1 — targets of popular weight-loss drugs like semaglutide — that are absent in humans.
“虽然司美格鲁肽等药物在肥胖治疗中取得了成功，但新一代疗法同时靶向GLP-1R和GIPR等多个受体。了解这些受体在人类下丘脑中的特定作用机制，对设计更安全、更有效的治疗方案至关重要。”来自马克斯·普朗克代谢研究所、曾任剑桥大学剑桥大学代谢科学研究所-代谢研究实验室（IMS-MRL）研究员的乔治娜·道塞特博士 (Georgina Dowsett) 指出。
"While drugs like semaglutide have shown success in treating obesity, newer therapies target multiple receptors such as GLP-1R and GIPR. Understanding how these receptors function specifically in the human hypothalamus is now crucial for designing safer and more effective treatments," said Dr Georgina Dowsett from the Max Planck Institute for Metabolism Research and formerly at the IMS-MRL.
“我们绘制的人类下丘脑图谱是基础研究与转化研究中的一项重要工具。”马克斯·普朗克代谢研究所所长延斯·C·布鲁宁教授 (Jens C. Brüning) 表示。“该图谱使我们能够精准识别哪些小鼠神经细胞与人类细胞最为相似，从而推动更具针对性的临床前研究。”
“Our map of the human hypothalamus is an essential tool for basic and translational research,” added Professor Jens C. Brüning, Director at the Max Planck Institute. “It allows us to pinpoint which mouse nerve cells are most comparable to human cells, enabling more targeted preclinical studies.”
HYPOMAP采用开放获取（Open-Access）形式，确保全球科学界都能共享这一宝贵资源。HYPOMAP不仅揭示了下丘脑在肥胖到恶病质（cachexia，一种涉及肌肉与脂肪极度消耗、常发生于多种严重疾病的消耗性综合征）等多种疾病中的作用，还为解决当今全球面临的重大健康挑战提供了研究基础。
HYPOMAP’s open-access nature ensures that it will be an invaluable resource for scientists worldwide. By offering insights into the hypothalamus’s role in conditions ranging from obesity to cachexia (a wasting condition associated with several illness, which involves extreme loss of muscle and fat), it provides a foundation for tackling some of the most pressing health challenges of our time.
“这仅仅是个开始。”论文的第一作者、Addenbrooke’s医院病理学顾问、剑桥大学代谢科学研究所-代谢研究实验室（IMS-MRL）的约翰·塔德罗斯博士 (John Tadross) 表示。“下丘脑图谱本身就是一个里程碑，但真正对患者产生深远影响的，是我们能否了解超重或体重不足人群的下丘脑的变化。这可能会从根本上改变我们对代谢健康的认知，并推动更加个性化的治疗方案。”
Dr John Tadross, Consultant Pathologist at Addenbrooke’s Hospital and lead author from IMS-MRL, said: “This is just the beginning. The atlas itself is a milestone, but what could really make a difference for patients is understanding how the hypothalamus changes in people who are overweight or underweight. This could fundamentally shift our approach to metabolic health and enable more personalised therapies.”
借助HYPOMAP，研究人员获得了一把解锁人类大脑代谢控制中心奥秘的新钥匙。通过深入理解人类下丘脑，科学界在对抗肥胖、二型糖尿病及相关代谢性疾病的道路上迈出了重要一步。
With HYPOMAP, researchers have a new tool to unlock the secrets of the human brain’s metabolic control centre. By better understanding the human hypothalamus, science takes a significant step toward combating obesity, type 2 diabetes, and related conditions.
