Metabolic diseases, including obesity, diabetes mellitus and cardiovascular disease, are a major threat to health in the modern world, but efforts to understand the underlying mechanisms and develop rational treatments are limited by the lack of appropriate human model systems. Notably, advances in stem cell and organoid technology allow the generation of cellular models that replicate the histological, molecular and physiological properties of human organs. Combined with marked improvements in gene editing tools, human stem cells and organoids provide unprecedented systems for studying mechanisms of metabolic diseases. Here, we review progress made over the past decade in the generation and use of stem cell-derived metabolic cell types and organoids in metabolic disease research, especially obesity and liver diseases. In particular, we discuss the limitations of animal models and the advantages of stem cells and organoids, including their application to metabolic diseases. We also discuss mechanisms of drug action, understanding the efficacy and toxicity of existing therapies, screening for new treatments and pursuing personalized therapies. We highlight the potential of combining stem cell-derived organoids with gene editing and functional genomics to revolutionize the approach to finding treatments for metabolic diseases.

代谢性疾病，包括肥胖、糖尿病和心血管疾病，是现代世界健康的主要威胁，但由于缺乏适当的人体模型系统，了解其潜在机制和开发合理治疗的努力受到限制。值得注意的是，干细胞和类器官技术的进步允许生成复制人体器官的组织学、分子和生理特性的细胞模型。结合基因编辑工具的显着改进，人类干细胞和类器官为研究代谢疾病的机制提供了前所未有的系统。在这里，我们回顾了过去十年在代谢疾病研究，特别是肥胖和肝病中产生和使用干细胞衍生的代谢细胞类型和类器官方面取得的进展。尤其是，我们讨论了动物模型的局限性以及干细胞和类器官的优势，包括它们在代谢性疾病中的应用。我们还讨论药物作用机制、了解现有疗法的功效和毒性、筛选新疗法和寻求个性化疗法。我们强调了将干细胞衍生的类器官与基因编辑和功能基因组学相结合的潜力，以彻底改变寻找代谢疾病治疗方法的方法。