Author, as appears in the article.: 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.;
Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques
URV's Author/s: Fernandez Veledo, Sonia / Vendrell Ortega, Juan José
Keywords: Tumor-suppressor activity Target Protein phosphatase 2a Pp2a regulatory subunit Phosphorylation Metabolic syndrome Gene-expression Fatty liver-disease Chrebp B56-gamma
Abstract: 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.
Thematic Areas: 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
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: sonia.fernandez@urv.cat juanjose.vendrell@urv.cat
Author identifier: 0000-0003-2906-3788 0000-0002-6994-6115
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005561
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Plos Genetics. 11 (10): e1005561-e1005561
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
Article's DOI: 10.1371/journal.pgen.1005561
Entity: Universitat Rovira i Virgili
Journal publication year: 2015
Publication Type: Journal Publications