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Hippo STK kinases drive metabolic derangement

Obesity is associated with mitochondrial dysfunction and chronic metabolic derailment. Cho et al. report that elevated adipose expression of the Hippo kinases STK3 and STK4 (STK3/4) in obesity and type 2 diabetes decreases the mass and oxidative capacity of adipocyte mitochondria. Genetic or pharmacological inhibition of STK3/4 restores mitochondrial mass and function in adipocytes and improves glucose homeostasis in mice with diet-induced obesity. These findings support STK3/4 as new targets for obesity-related diseases.

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Fig. 1: Inhibition of the Hippo kinases STK3/4 in therapy for metabolic disease.


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This work was supported by grants from the German Research Foundation (DFG) and JDRF.

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Correspondence to Kathrin Maedler or Amin Ardestani.

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The authors hold the shared patent WO2016210345A1: Composition and methods for inhibiting mammalian sterile 20-like kinase 1.

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Maedler, K., Ardestani, A. Hippo STK kinases drive metabolic derangement. Nat Metab 3, 295–296 (2021).

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