Ghrelin Requires p53 to Stimulate Lipid Storage in Fat and Liver

• Published in: Endocrinology (Philadelphia) Vol. 154; no. 10; pp. 3671 - 3679
• Main Authors: Porteiro, Begoña, Díaz-Ruíz, Alberto, Martínez, Gloria, Senra, Ana, Vidal, Anxo, Serrano, Manuel, Gualillo, Oreste, López, Miguel, Malagón, María M, Diéguez, Carlos, Nogueiras, Rubén
• Format: Journal Article
• Language: English
• Published: Chevy Chase, MD Endocrine Society 01.10.2013
• Subjects: Adipogenesis; Adipose Tissue, White - enzymology; Adipose Tissue, White - metabolism; Adipose Tissue, White - pathology; Adiposity; Animals; Biological and medical sciences; Crosses, Genetic; Enzyme Induction; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Ghrelin - administration & dosage; Ghrelin - metabolism; Injections, Intraperitoneal; Lipogenesis; Liver - enzymology; Liver - metabolism; Liver - pathology; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Obesity - blood; Obesity - etiology; Obesity - metabolism; Obesity - pathology; Tissue Culture Techniques; Triglycerides - blood; Triglycerides - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Vertebrates: endocrinology; Weight Gain; Lipids; Storage; Digestive system; Ghrelin; Liver; p53 Protein
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2013-1176

Ghrelin, a stomach-derived peptide, stimulates feeding behavior and adiposity. For its orexigenic action, ghrelin triggers a central SIRT1/p53/AMPK pathway. The tumor suppressor p53 also plays an important role in white adipose tissue (WAT), where it is up-regulated in the adipocytes of obese mice. It is not known, however, whether p53 has any role in mediating the peripheral action of ghrelin. In the present study, chronic peripheral ghrelin treatment resulted in increased body weight and fat-mass gain in wild-type mice. Correspondingly, mRNA levels of several adipogenic and fat-storage-promoting enzymes were up-regulated in WAT, whereas hepatic triglyceride content and lipogenic enzymes were also increased in wild-type mice following ghrelin treatment. In contrast, mice lacking p53 failed to respond to ghrelin treatment, with their body weight, fat mass, and adipocyte and hepatic metabolism remaining unchanged. Thus, our results show that p53 is necessary for the actions of ghrelin on WAT and liver, leading to changes in expression levels of lipogenic and adipogenic genes, and modifying body weight.