Article (Scientific journals)
Dual‑specificity phosphatase 3 deletion promotes obesity, non‑alcoholic steatohepatitis and hepatocellular carcinoma
Jacques, Sophie; Arjomand, Arash; Perée, Hélène et al.
2021In Scientific Reports, 11, p. 5817
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Abstract :
[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
Author, co-author :
Jacques, Sophie 
Arjomand, Arash 
Perée, Hélène  ;  Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics
COLLINS, Patrick ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service dermatopathologie
Mayer, Alice  ;  Université de Liège - ULiège > GIGA Platform Genomics
Lavergne, Arnaud  ;  Université de Liège - ULiège > GIGA Platform Genomics
Wéry, Marie ;  Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics
Mni, Myriam ;  Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics
Hego, Alexandre ;  Université de Liège - ULiège > GIGA Platform Imaging & Flow cytometry
Thuillier, Virginie ;  Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics
Bahri, Mohamed Ali  ;  Université de Liège - ULiège > GIGA CRC In vivo Imaging - Aging & Memory
Plenevaux, Alain  ;  Université de Liège - ULiège > GIGA CRC In vivo Imaging - Preclinical Imaging
Di Valentin, Emmanuel  ;  Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
Oury, Cécile  ;  Université de Liège - ULiège > GIGA Cardiovascular Sciences - Cardiology
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
More authors (9 more) Less
Language :
English
Title :
Dual‑specificity phosphatase 3 deletion promotes obesity, non‑alcoholic steatohepatitis and hepatocellular carcinoma
Publication date :
2021
Journal title :
Scientific Reports
eISSN :
2045-2322
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
11
Pages :
5817
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 12 April 2021

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