2026-04-27T08:02:39Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/112802024-09-27T08:51:09Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Fuster, Jose J. author Zuriaga, María A author Zorita, Virginia author MacLauchlan, Susan author Polackal, Maya N author Viana-Huete, Vanesa author Ferrer-Pérez, Alba author Matesanz, Nuria author Herrero-Cervera, Andrea author Sano, Soichi author Cooper, Matthew A author González-Navarro, Herminia author Walsh, Kenneth author 2020-10-27 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-1β in white adipose tissue, and it is suppressed by pharmacological inhibition of NLRP3 inflammasome-mediated IL-1β production. These findings support a causal contribution of somatic TET2 mutations to insulin resistance and type 2 diabetes. Cell Rep. 2020; 33(4):108326 2211-1247 http://hdl.handle.net/20.500.12105/11280 33113366 10.1016/j.celrep.2020.108326 Cell reports TET2-Loss-of-Function-Driven Clonal Hematopoiesis Exacerbates Experimental Insulin Resistance in Aging and Obesity.