Autor según el artículo: Cheng, Yong-Sheng; Seibert, Oksana; Kloeting, Nora; Dietrich, Arne; Strassburger, Katrin; Fernandez-Veledo, Sonia; Vendrell, Joan J.; Zorzano, Antonio; Blueher, Matthias; Herzig, Stephan; Diaz, Mauricio Berriel; Teleman, Aurelio A.;
Departamento: Medicina i Cirurgia Ciències Mèdiques Bàsiques
Autor/es de la URV: Fernandez Veledo, Sonia / Vendrell Ortega, Juan José
Palabras clave: Tumor-suppressor activity Target Protein phosphatase 2a Pp2a regulatory subunit Phosphorylation Metabolic syndrome Gene-expression Fatty liver-disease Chrebp B56-gamma
Resumen: In mammals, the liver plays a central role in maintaining carbohydrate and lipid homeostasis by acting both as a major source and a major sink of glucose and lipids. In particular, when dietary carbohydrates are in excess, the liver converts them to lipids via de novo lipogenesis. The molecular checkpoints regulating the balance between carbohydrate and lipid homeostasis, however, are not fully understood. Here we identify PPP2R5C, a regulatory subunit of PP2A, as a novel modulator of liver metabolism in postprandial physiology. Inactivation of PPP2R5C in isolated hepatocytes leads to increased glucose uptake and increased de novo lipogenesis. These phenotypes are reiterated in vivo, where hepatocyte specific PPP2R5C knockdown yields mice with improved systemic glucose tolerance and insulin sensitivity, but elevated circulating triglyceride levels. We show that modulation of PPP2R5C levels leads to alterations in AMPK and SREBP-1 activity. We find that hepatic levels of PPP2R5C are elevated in human diabetic patients, and correlate with obesity and insulin resistance in these subjects. In sum, our data suggest that hepatic PPP2R5C represents an important factor in the functional wiring of energy metabolism and the maintenance of a metabolically healthy state.
Áreas temáticas: Zootecnia / recursos pesqueiros Saúde coletiva Química Odontología Molecular biology Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Geociências Genetics (clinical) Genetics & heredity Genetics Filosofia/teologia:subcomissão filosofia Farmacia Engenharias iv Educação física Ecology, evolution, behavior and systematics Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Ciência da computação Cancer research Biotecnología Biodiversidade Astronomia / física Antropologia / arqueologia
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: sonia.fernandez@urv.cat juanjose.vendrell@urv.cat
Identificador del autor: 0000-0003-2906-3788 0000-0002-6994-6115
Fecha de alta del registro: 2024-09-07
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005561
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Plos Genetics. 11 (10): e1005561-e1005561
Referencia de l'ítem segons les normes APA: Cheng, Yong-Sheng; Seibert, Oksana; Kloeting, Nora; Dietrich, Arne; Strassburger, Katrin; Fernandez-Veledo, Sonia; Vendrell, Joan J.; Zorzano, Antonio (2015). PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis. Plos Genetics, 11(10), e1005561-e1005561. DOI: 10.1371/journal.pgen.1005561
DOI del artículo: 10.1371/journal.pgen.1005561
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2015
Tipo de publicación: Journal Publications