Single-cell insights into obesity: cellular mechanisms across metabolic organs

Obesity is a serious public health concern worldwide that can lead to a series of metabolic complications and greatly impair life quality. During obesity, excessive lipid deposition introduces significant stress into the cellular microenvironment, resulting in widespread low-grade inflammation throughout the body, which eventually causes functional defects in various tissues/organs. Developing effective treatment approaches to obesity and its complications requires an in-depth understanding of the cellular mechanisms underlying the maladaptation across distinct organs. Single-cell RNA sequencing (scRNA-seq) has revolutionized our knowledge of cell heterogeneity and greatly advanced the studies focusing on etiology and progression of various tissue dysfunctions in diet-induced obesity at single-cell level. In this review, we summarize recent scRNA-seq studies investigating the effects of diet-induced obesity on distinct cell populations across diverse metabolic organs, including the intestine, liver, adipose tissue, pancreatic islets, and aorta, which provide detailed information on cellular identity reprogramming, metabolic function alterations, and intercellular communications. These single-cell insights highlight the initial adaptation to ultimately dysfunctional process of diverse cell populations in those organs to the lipid-overloading environment, thereby offering valuable targets for future therapeutic intervention.