Targeting ERK3/MK5 complex for treatment of obesity and diabetes

Angel Loza-Valdes, Rabih El-Merahbi, Toufic Kassouf, Agnieszka Demczuk, Saskia Reuter, Jonathan Trujillo Viera, Till Karwen, Minhe Noh, Mona C. Löffler, Rafael Romero-Becerra, Jorge L. Torres, Miguel Marcos, Guadalupe Sabio, Urszula Wojda, Grzegorz Sumara*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)119-125
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume612
DOIs
Publication statusPublished - 5 Jul 2022
Externally publishedYes

Keywords

  • adipocytes
  • cellular respiration
  • diabetes
  • ERK3 (MAPK6)
  • GLPG0259
  • lipolysis
  • MAPK-activated protein kinase 5 (MK5)
  • obesity

Fingerprint

Dive into the research topics of 'Targeting ERK3/MK5 complex for treatment of obesity and diabetes'. Together they form a unique fingerprint.

Cite this