| First Author | Fuster JJ | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 4 | Pages | 108326 |
| PubMed ID | 33113366 | Mgi Jnum | J:300596 |
| Mgi Id | MGI:6489091 | Doi | 10.1016/j.celrep.2020.108326 |
| Citation | Fuster JJ, et al. (2020) TET2-Loss-of-Function-Driven Clonal Hematopoiesis Exacerbates Experimental Insulin Resistance in Aging and Obesity. Cell Rep 33(4):108326 |
| abstractText | Human aging is frequently accompanied by the acquisition of somatic mutations in the hematopoietic system that induce clonal hematopoiesis, leading to the development of a mutant clone of hematopoietic progenitors and leukocytes. This somatic-mutation-driven clonal hematopoiesis has been associated with an increased incidence of cardiovascular disease and type 2 diabetes, but whether this epidemiological association reflects a direct, causal contribution of mutant hematopoietic and immune cells to age-related metabolic abnormalities remains unexplored. Here, we show that inactivating mutations in the epigenetic regulator TET2, which lead to clonal hematopoiesis, aggravate age- and obesity-related insulin resistance in mice. This metabolic dysfunction is paralleled by increased expression of the pro-inflammatory cytokine IL-1beta in white adipose tissue, and it is suppressed by pharmacological inhibition of NLRP3 inflammasome-mediated IL-1beta production. These findings support a causal contribution of somatic TET2 mutations to insulin resistance and type 2 diabetes. |
