β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development
Menée sur des souris ayant reçu une alimentation de type occidental ou riche en graisses, cette étude met en évidence l'intérêt de cibler la spectrine bêta 2 pour prévenir les maladies hépatiques liées au régime alimentaire ainsi que le développement d'un cancer du foie
The prevalence of nonalcoholic steatohepatitis (NASH) and liver cancer is increasing. De novo lipogenesis and fibrosis contribute to disease progression and cancerous transformation. Here, we found that
β2-spectrin (SPTBN1) promotes sterol regulatory element (SRE)
–binding protein (SREBP)–stimulated lipogenesis and development of liver cancer in mice fed a high-fat diet (HFD) or a western diet (WD). Either hepatocyte-specific knockout of SPTBN1 or siRNA-mediated therapy protected mice from HFD/WD-induced obesity and fibrosis, lipid accumulation, and tissue damage in the liver. Biochemical analysis suggested that HFD/WD induces SPTBN1 and SREBP1 cleavage by CASPASE-3 and that the cleaved products interact to promote expression of genes with sterol response elements. Analysis of human NASH tissue revealed increased SPTBN1 and CASPASE-3 expression. Thus, our data indicate that SPTBN1 represents a potential target for therapeutic intervention in NASH and liver cancer.