| First Author | Wang L | Year | 2022 |
| Journal | Cell Metab | Volume | 34 |
| Issue | 1 | Pages | 75-89.e8 |
| PubMed ID | 34813734 | Mgi Jnum | J:321716 |
| Mgi Id | MGI:6875517 | Doi | 10.1016/j.cmet.2021.11.002 |
| Citation | Wang L, et al. (2022) Targeting p21(Cip1) highly expressing cells in adipose tissue alleviates insulin resistance in obesity. Cell Metab 34(1):75-89.e8 |
| abstractText | 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-kappaB pathway within p21(high) cells, without killing them, attenuates insulin resistance. Moreover, fat transplantation experiments establish that p21(high) cells within fat are sufficient to cause insulin resistance in vivo. Importantly, a senolytic cocktail, dasatinib plus quercetin, eliminates p21(high) cells in human fat ex vivo and mitigates insulin resistance following xenotransplantation into immuno-deficient mice. Our findings lay the foundation for pursuing the targeting of p21(high) cells as a new therapy to alleviate insulin resistance. |
