Author, as appears in the article.: Montori-Grau M; Pedreira-Casahuga R; Boyer-Díaz Z; Lassot I; García-Martínez C; Orozco A; Cebrià J; Osorio-Conles O; Chacón M; Vendrell J; Vázquez-Carrera M; Desagher S; Jiménez-Chillarón J; Gómez-Foix A

Department: Medicina i Cirurgia

URV's Author/s: Vendrell Ortega, Juan José

Keywords: Trim7: trim7 isoform 4 Synthase kinase-3 Skeletal muscle Protein Gnip1: trim7 isoform 1 Glycogen metabolism Glucose-uptake Adenovirus-mediated transfer Activation skeletal muscle gnip1: trim7 isoform 1 glycogen metabolism

Abstract: Glycogenin-interacting protein 1 (GNIP1) is a tripartite motif (TRIM) protein with E3 ubiquitin ligase activity that interacts with glycogenin. These data suggest that GNIP1 could play a major role in the control of glycogen metabolism. However, direct evidence based on functional analysis remains to be obtained.The aim of this study was 1) to define the expression pattern of glycogenin-interacting protein/Tripartite motif containing protein 7 (GNIP/TRIM7) isoforms in humans, 2) to test their ubiquitin E3 ligase activity, and 3) to analyze the functional effects of GNIP1 on muscle glucose/glycogen metabolism both in human cultured cells and in vivo in mice.We show that GNIP1 was the most abundant GNIP/TRIM7 isoform in human skeletal muscle, whereas in cardiac muscle only TRIM7 was expressed. GNIP1 and TRIM7 had autoubiquitination activity in vitro and were localized in the Golgi apparatus and cytosol respectively in LHCN-M2 myoblasts. GNIP1 overexpression increased glucose uptake in LHCN-M2 myotubes. Overexpression of GNIP1 in mouse muscle in vivo increased glycogen content, glycogen synthase (GS) activity and phospho-GSK-3?/? (Ser21/9) and phospho-Akt (Ser473) content, whereas decreased GS phosphorylation in Ser640. These modifications led to decreased blood glucose levels, lactate levels and body weight, without changing whole-body insulin or glucose tolerance in mouse.GNIP1 is an ubiquitin ligase with a markedly glycogenic effect in skeletal muscle.Copyright © 2018 Elsevier Inc. All rights reserved.

Thematic Areas: Saúde coletiva Odontología Nutrição Medicina iii Medicina ii Medicina i Interdisciplinar General medicine Farmacia Engenharias ii Enfermagem Endocrinology, diabetes and metabolism Endocrinology & metabolism Endocrinology Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciência de alimentos Biotecnología Antropologia / arqueologia

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 00260495

Author's mail: juanjose.vendrell@urv.cat

Author identifier: 0000-0002-6994-6115

Record's date: 2023-02-18

Papper version: info:eu-repo/semantics/acceptedVersion

Link to the original source: https://www.metabolismjournal.com/article/S0026-0495(18)30044-1/fulltext

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Metabolism-Clinical And Experimental. 83 177-187

APA: Montori-Grau M; Pedreira-Casahuga R; Boyer-Díaz Z; Lassot I; García-Martínez C; Orozco A; Cebrià J; Osorio-Conles O; Chacón M; Vendrell J; Vázquez-Car (2018). GNIP1 E3 ubiquitin ligase is a novel player in regulating glycogen metabolism in skeletal muscle. Metabolism-Clinical And Experimental, 83(), 177-187. DOI: 10.1016/j.metabol.2018.02.005

Article's DOI: 10.1016/j.metabol.2018.02.005

Entity: Universitat Rovira i Virgili

Journal publication year: 2018

Publication Type: Journal Publications