2026-07-21T16:29:04Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/157382024-09-27T09:37:16Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Loza-Valdes, Angel author El-Merahbi, Rabih author Kassouf, Toufic author Demczuk, Agnieszka author Reuter, Saskia author Viera, Jonathan Trujillo author Karwen, Till author Noh, Minhe author Löffler, Mona C author Romero-Becerra, Rafael author Torres, Jorge L author Marcos, Miguel author Sabio, Guadalupe author Wojda, Urszula author Sumara, Grzegorz author 2022-07-05 Kinases represent one of the largest druggable families of proteins. Importantly, many kinases are aberrantly activated/de-activated in multiple organs during obesity, which contributes to the development of diabetes and associated diseases. Previous results indicate that the complex between Extracellular-regulated kinase 3 (ERK3) and Mitogen-Activated Protein Kinase (MAPK)-activated protein kinase 5 (MK5) suppresses energy dissipation and promotes fatty acids (FAs) output in adipose tissue and, therefore promotes obesity and diabetes. However, the therapeutic potential of targeting this complex at the systemic level has not been fully explored. Here we applied a translational approach to target the ERK3/MK5 complex in mice. Importantly, deletion of ERK3 in the whole body or administration of MK5-specific inhibitor protects against obesity and promotes insulin sensitivity. Finally, we show that the expression of ERK3 and MK5 correlates with the degree of obesity and that ERK3/MK5 complex regulates energy dissipation in human adipocytes. Altogether, we demonstrate that ERK3/MK5 complex can be targeted in vivo to preserve metabolic health and combat obesity and diabetes. Biochem Biophys Res Commun. 2022 Jul 5;612:119-125 10.1016/j.bbrc.2022.04.070 1090-2104 Biochemical and biophysical research communications 35523049 http://hdl.handle.net/20.500.12105/15738 Targeting ERK3/MK5 complex for treatment of obesity and diabetes.