[en] Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western
countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe
and progressive non-alcoholic steatohepatitis (NASH) that can lead to hepatocellular carcinoma
(HCC). Obesity and related metabolic syndrome are important risk factors for the development of
NAFLD, NASH and HCC. DUSP3 is a small dual-specificity protein phosphatase with a poorly known
physiological function. We investigated its role in metabolic syndrome manifestations and in HCC
using a mouse knockout (KO) model. While aging, DUSP3-KO mice became obese, exhibited insulin
resistance, NAFLD and associated liver damage. These phenotypes were exacerbated under high
fat diet (HFD). In addition, DEN administration combined to HFD led to rapid HCC development
in DUSP3-KO compared to wild type (WT) mice. DUSP3-KO mice had more serum triglycerides,
cholesterol, AST and ALT compared to control WT mice under both regular chow diet (CD) and HFD.
The level of fasting insulin was higher compared to WT mice, though, fasting glucose as well as
glucose tolerance were normal. At the molecular level, HFD led to decreased expression of DUSP3 in
WT mice. DUSP3 deletion was associated with increased and consistent phosphorylation of the insulin
receptor (IR) and with higher activation of the downstream signaling pathway. In conclusion, our
results support a new role for DUSP3 in obesity, insulin resistance, NAFLD and liver damage.
Disciplines :
Life sciences: Multidisciplinary, general & others
MOUTSCHEN, Michel ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service des maladies infectieuses - médecine interne
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Paquot, Nicolas ; Université de Liège - ULiège > Département des sciences de la santé publique > Diabétologie, nutrition et maladies métaboliques
Rahmouni, Souad ; Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics
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