Ghrelin Requires p53 to Stimulate Lipid Storage in Fat and Liver

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....

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Published in:Endocrinology (Philadelphia) 2013-10, Vol.154 (10), p.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: Article
Language:English
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
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Summary: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.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2013-1176