Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/2220
Title: Adipose tissue glycogen accumulation is associated with obesity-linked inflammation in humans.
Authors: Ceperuelo-Mallafré, Victoria
Ejarque, Miriam
Serena, Carolina
Durán, Xavier
Montori-Grau, Marta
Rodríguez, Miguel Ángel
Yanes, Óscar
Núñez-Roa, Catalina
Roche, Kelly
Puthanveetil, Prasanth
Garrido-Sánchez, Lourdes
Sáez, Enrique
Tinahones, Francisco J
García-Roves, Pablo M
Gómez-Foix, Anna Ma
Saltiel, Alan R
Vendrell, Joan
Fernández-Veledo, Sonia
metadata.dc.contributor.authoraffiliation: [Ceperuelo-Mallafré,V; Ejarque,M; Serena,C; Núñez-Roa,C; Roche,K; Vendrell,J; Fernández-Veledo,S] Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain. [Ceperuelo-Mallafré,V; Ejarque,M; Serena,C; Durán,X; Montori-Grau,M; Rodríguez,MA; Yánes,O; Núñez-Roa,C; Roche,K; Gómez-Foix,AM; Vendrell,J; Fernández-Veledo,S] CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. [Montori-Grau,M] Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. [Rodríguez,MA] Centre for Omic Sciences (COS), Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain. [Yanes,O] Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona, Spain. [Puthanveetil,P; Saltiel,AR] Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA. [Garrido-Sánchez,L; Tinahones,FJ] Hospital Universitario Virgen de la Victoria, Instituto de Investigaciones Biomédicas de Málaga (IBIMA), Universidad de Málaga, IBIMA, Spain. [Garrido-Sánchez,L; Tinahones,FJ] CIBER de Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Sáez,E] Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA. [García-Roves,PM] Departamento de Ciencias Fisiológicas II, Facultad de Medicina, Universitat de Barcelona, Barcelona, Spain.
Keywords: Glycogen;Adipocyte;Macrophage;Autophagy;Obesity;Insulin resistance;Adipocitos;Animales;Índice de masa corporal;Glucosa;Glucógeno sintasa;Resistencia a la insulina;Espectroscopía de Resonancia Magnética;Espectrometría de Masas;Masculino;Ratón;Estrés fisiológico;Obesidad;Grasa subcutánea;Serina-Treonina Quinasas TOR;Humanos
metadata.dc.subject.mesh: Medical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Adipocytes
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Autophagy
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index
Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Glycosyltransferases::Hexosyltransferases::Glucosyltransferases::Glycogen Synthase
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin Resistance
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Spectrum Analysis::Magnetic Resonance Spectroscopy
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Stress, Physiological
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue, White::Subcutaneous Fat
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::TOR Serine-Threonine Kinases
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Issue Date: Jan-2016
Publisher: Elsevier
Citation: Ceperuelo-Mallafré V, Ejarque M, Serena C, Durán X, Montori-Grau M, Rodríguez MA, et al. Adipose tissue glycogen accumulation is associated with obesity-linked inflammation in humans. Mol Metab. 2016; 5(1):5-18
Abstract: OBJECTIVE Glycogen metabolism has emerged as a mediator in the control of energy homeostasis and studies in murine models reveal that adipose tissue might contain glycogen stores. Here we investigated the physio(patho)logical role of glycogen in human adipose tissue in the context of obesity and insulin resistance. METHODS We studied glucose metabolic flux of hypoxic human adipoctyes by nuclear magnetic resonance and mass spectrometry-based metabolic approaches. Glycogen synthesis and glycogen content in response to hypoxia was analyzed in human adipocytes and macrophages. To explore the metabolic effects of enforced glycogen deposition in adipocytes and macrophages, we overexpressed PTG, the only glycogen-associated regulatory subunit (PP1-GTS) reported in murine adipocytes. Adipose tissue gene expression analysis was performed on wild type and homozygous PTG KO male mice. Finally, glycogen metabolism gene expression and glycogen accumulation was analyzed in adipose tissue, mature adipocytes and resident macrophages from lean and obese subjects with different degrees of insulin resistance in 2 independent cohorts. RESULTS We show that hypoxia modulates glucose metabolic flux in human adipocytes and macrophages and promotes glycogenesis. Enforced glycogen deposition by overexpression of PTG re-orients adipocyte secretion to a pro-inflammatory response linked to insulin resistance and monocyte/lymphocyte migration. Furthermore, glycogen accumulation is associated with inhibition of mTORC1 signaling and increased basal autophagy flux, correlating with greater leptin release in glycogen-loaded adipocytes. PTG-KO mice have reduced expression of key inflammatory genes in adipose tissue and PTG overexpression in M0 macrophages induces a pro-inflammatory and glycolytic M1 phenotype. Increased glycogen synthase expression correlates with glycogen deposition in subcutaneous adipose tissue of obese patients. Glycogen content in subcutaneous mature adipocytes is associated with BMI and leptin expression. CONCLUSION Our data establish glycogen mishandling in adipose tissue as a potential key feature of inflammatory-related metabolic stress in human obesity.
Description: Journal Article;
URI: http://hdl.handle.net/10668/2220
metadata.dc.relation.publisherversion: http://www.sciencedirect.com/science/article/pii/S2212877815001969
metadata.dc.identifier.doi: 10.1016/j.molmet.2015.10.001
ISSN: 2212-8778 (Online)
Appears in Collections:01- Artículos - Hospital Virgen de la Victoria
01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga

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