Hepatocyte p53 ablation induces metabolic dysregulation that is corrected by food restriction and vertical sleeve gastrectomy in mice.

ABSTRACT: P53 has been implicated in the pathogenesis of obesity and diabetes; however, the mechanisms and tissue sites of action are incompletely defined. Therefore, we investigated the role of hepatocyte p53 in metabolic homeostasis using a hepatocyte-specific p53 knockout mouse model. To gain further mechanistic insight, we studied mice under two complementary conditions of restricted weight gain: vertical sleeve gastrectomy (VSG) or food restriction. VSG or sham surgery was performed in high-fat diet-fed male hepatocyte-specific p53 wild-type and knockout littermates. Sham-operated mice were fed ad libitum or food restricted to match their body weight to VSG-operated mice. Hepatocyte-specific p53 ablation in sham-operated ad libitum-fed mice impaired glucose homeostasis, increased body weight, a

SUBMITTER: Holter MM 

PROVIDER: S-EPMC8884714 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature