Targeting p21^Cip1 highly expressing cells in adipose tissue alleviates insulin resistance in obesity.

ABSTRACT: Insulin resistance is a pathological state often associated with obesity, representing a major risk factor for type 2 diabetes. Limited mechanism-based strategies exist to alleviate insulin resistance. Here, using single-cell transcriptomics, we identify a small, critically important, but previously unexamined cell population, p21^Cip1 highly expressing (p21^high) cells, which accumulate in adipose tissue with obesity. By leveraging a p21-Cre mouse model, we demonstrate that intermittent clearance of p21^high cells can both prevent and alleviate insulin resistance in obese mice. Exclusive inactivation of the NF-κB pathway within p21^high cells, without killing them, attenuates insulin resistance. Moreover, fat transplantation experiments establish th

SUBMITTER: Wang L 

PROVIDER: S-EPMC8732323 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature