01850nas a2200193   4500000000100000000000100001008004100002260001200043653001500055653002700070100001600097700002200113245008200135856005500217300001200272490000700284520135100291022001401642       2022                            d  c2022-1210aMetabolism10aPluripotent Stem Cells1 aWenxiang Hu1 aMitchell A. Lazar00aModelling metabolic diseases and drug response using stem cells and organoids  uhttps://www.nature.com/articles/s41574-022-00733-z  a744-7590 v183 aMetabolic 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.  a1759-5037