Dual-specificity-phosphatase 3 (DUSP3) deletion promotes liver inflammation and high fat diet-induced hepatocellular carcinoma

Overweight and obesity are considered as risk factors for hepatocellular carcinoma
(HCC) development. The mechanisms by which obesity promotes liver inflammation
are however poorly understood. We recently generated a full DUSP3 knockout (KO)
mouse. The obtained mice were born normal with no spontaneous phenotype.
However, while aging, DUSP3-KO mice became obese and developed
hepatosteatosis. The phenotype was exacerbated under high fat diet (HFD).
Furthermore, when treated with diethylnitrosamine (DEN) procarcinogen, DUSP3-KO
mice developed HCC faster than WT littermates. The combination of DEN with HFD
accelerated the onset of HCC development in these mice compared to WT mice. This
was associated with increased systemic levels of several metabolites and with
hyperphosphorylation of the insulin-like growth factor receptor I.