Inhibition of GCKIII kinases STK25 and MST3 mitigates organ lipotoxicity and enhances metabolic resilience under nutritional stress.

ABSTRACT:

Background

Obesity has reached pandemic proportions, highlighting the urgent need for continued research to uncover the molecular mechanisms governing lipid homeostasis and ectopic fat deposition in overnutrition. Our recent translational studies demonstrated that STE20-type kinases STK25 and MST3 associate with intracellular lipid droplets and play a pivotal role in regulating the dynamic balance between fat storage and utilization. This study aimed to assess the in vivo effects of the combined inhibition of STK25 and MST3 in obese mice.

Methods

We performed phenotypic characterization in three cohorts of mice fed a high-fat diet: (1) mice with genetic ablation of Stk25, (2) mice treated with Mst3-targeting antisense oligonucleotide (ASO), and (3) mice depleted of both STK2

SUBMITTER: Andersson E 

PROVIDER: S-EPMC12455811 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature