Targeting ERK3/MK5 complex for treatment of obesity and diabetes

• DOI: 10.1016/j.bbrc.2022.04.070
• Publication Date: 2022-04-27T14:53:37Z
• Authors: Angel Loza-Valdes; Rabih El-Merahbi; Toufic Kassouf; Agnieszka Demczuk; Saskia Reuter; Jonathan Trujillo...; Till Karwen; Minhe Noh; Mona C. Löffler; Rafael Romero-Bec...; Jorge L. Torres; Miguel Marcos; Guadalupe Sabio; Urszula Wojda; Grzegorz Sumara
• Keywords: Druggability

Kinases represent one of the largest druggable families proteins. Importantly, many kinases are aberrantly activated/de-activated in multiple organs during obesity, which contributes to development diabetes and associated diseases. Previous results indicate that complex between Extracellular-regulated kinase 3 (ERK3) Mitogen-Activated Protein Kinase (MAPK)-activated protein 5 (MK5) suppresses energy dissipation promotes fatty acids (FAs) output adipose tissue and, therefore obesity diabetes. However, therapeutic potential targeting this at systemic level has not been fully explored. Here we applied a translational approach target ERK3/MK5 mice. deletion ERK3 whole body or administration MK5-specific inhibitor protects against insulin sensitivity. Finally, show expression MK5 correlates with degree regulates human adipocytes. Altogether, demonstrate can be targeted vivo preserve metabolic health combat