Articles producció científica> Medicina i Cirurgia

PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis

  • Dades identificatives

    Identificador: imarina:5130454
    Autors:
    Cheng, Yong-ShengSeibert, OksanaKloeting, NoraDietrich, ArneStrassburger, KatrinFernandez-Veledo, SoniaVendrell, Joan J.Zorzano, AntonioBlueher, MatthiasHerzig, StephanDiaz, Mauricio BerrielTeleman, Aurelio A.
    Resum:
    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.
  • Altres:

    Autor segons l'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.;
    Departament: Medicina i Cirurgia Ciències Mèdiques Bàsiques
    Autor/s de la URV: Fernandez Veledo, Sonia / Vendrell Ortega, Juan José
    Paraules clau: Tumor-suppressor activity Target Protein phosphatase 2a Pp2a regulatory subunit Phosphorylation Metabolic syndrome Gene-expression Fatty liver-disease Chrebp B56-gamma
    Resum: 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.
    Àrees temàtiques: 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
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    Adreça de correu electrònic de l'autor: sonia.fernandez@urv.cat juanjose.vendrell@urv.cat
    Identificador de l'autor: 0000-0003-2906-3788 0000-0002-6994-6115
    Data d'alta del registre: 2024-09-07
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005561
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Plos Genetics. 11 (10): e1005561-e1005561
    Referència 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 de l'article: 10.1371/journal.pgen.1005561
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2015
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Cancer Research,Ecology, Evolution, Behavior and Systematics,Genetics,Genetics & Heredity,Genetics (Clinical),Molecular Biology
    Tumor-suppressor activity
    Target
    Protein phosphatase 2a
    Pp2a regulatory subunit
    Phosphorylation
    Metabolic syndrome
    Gene-expression
    Fatty liver-disease
    Chrebp
    B56-gamma
    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
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