Year: 2016
Type: article
Abstract: p53 is well known for its tumor suppressor role, but this protein also has a poorly understood role in the regulation of metabolism. Human studies have implicated a common polymorphism at codon 72 of p53 in diabetic and pre-diabetic phenotypes. To understand this role, we utilized a humanized mouse model of the p53 codon 72 variants and monitored these mice following challenge with a high-fat diet (HFD). Mice with the arginine 72 (R72) variant of p53 developed more-severe obesity and glucose intolerance on a HFD, compared to mice with the proline 72 variant (P72). R72 mice developed insulin resistance, islet hypertrophy, increased infiltration of immune cells, and fatty liver disease. Gene expression analyses and studies with small-molecule inhibitors indicate that the p53 target genes Tnf and Npc1l1 underlie this phenotype. These results shed light on the role of p53 in obesity, metabolism, and inflammation.
Source: Cell Reports
Institutions: The Wistar Institute, University of Pennsylvania
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: G1364608215, G1390870092, G351856440, p53 Variants in Cancer Risk and Therapy, G499207949, G5517234272, G683675403, University of Pennsylvania Diabetes Research Center, Functional Analysis of p53 Polymorphic Variants, Consolidated Basic Cancer Research Program, Center for Molecular Studies in Digestive and Liver Diseases
OpenAlex ID: W2292304354