title: Ghrelin requires p53 to stimulate lipid storage in fat and liver.
abstract: 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.
authors.affiliation: Department of Physiology, Centre of Research in Molecular Medicine and Chronic Diseases of the University of Santiago de Compostela (CIMUS), University of Santiago de Compostela-Instituto de Investigación Sanitaria, Avda Barcelona s/n, 15782, Santiago de Compostela (A Coruña), Spain, and CIBER "Fisiopatología de la Obesidad y Nutrición," Instituto de Salud Carlos III, Spain. ruben.nogueiras@usc.es.
authors.forename: Begoña
authors.initials: B
authors.lastname: Porteiro
authors.forename: Alberto
authors.initials: A
authors.lastname: Díaz-Ruíz
authors.forename: Gloria
authors.initials: G
authors.lastname: Martínez
authors.forename: Ana
authors.initials: A
authors.lastname: Senra
authors.forename: Anxo
authors.initials: A
authors.lastname: Vidal
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
authors.forename: Oreste
authors.initials: O
authors.lastname: Gualillo
authors.forename: Miguel
authors.initials: M
authors.lastname: López
authors.forename: María M
authors.initials: MM
authors.lastname: Malagón
authors.forename: Carlos
authors.initials: C
authors.lastname: Diéguez
authors.forename: Rubén
authors.initials: R
authors.lastname: Nogueiras
mesh_terms: D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D050154:Adiposity; D000818:Animals; D003433:Crosses, Genetic; D004790:Enzyme Induction; D005260:Female; D020869:Gene Expression Profiling; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D050155:Lipogenesis; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D046509:Tissue Culture Techniques; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain
chemical_list: D054439:Ghrelin; D014280:Triglycerides; D016159:Tumor Suppressor Protein p53