Autor según el artículo: Ceperuelo-Mallafré V; Ejarque M; Serena C; Duran X; Montori-Grau M; Rodríguez MA; Yanes O; Núñez-Roa C; Roche K; Puthanveetil P; Garrido-Sánchez L; Saez E; Tinahones FJ; Garcia-Roves PM; Gómez-Foix AM; Saltiel AR; Vendrell J; Fernández-Veledo S

Departamento: Ciències Mèdiques Bàsiques Medicina i Cirurgia Enginyeria Electrònica, Elèctrica i Automàtica

Autor/es de la URV: Fernandez Veledo, Sonia / Vendrell Ortega, Juan José / Yanes Torrado, Óscar

Palabras clave: Targeting subunits Retinal-pigment epithelium Proinflammatory cytokine Obesity Necrosis-factor-alpha Macrophage Lipid-metabolism Insulin-resistance Insulin resistance Glycogen Glucose-transport Endoplasmic-reticulum stress Diabetes Binding domain Autophagy Adipose tissue Adipocyte Activated protein-kinase macrophage insulin resistance glycogen autophagy adipocyte

Resumen: 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.

Áreas temáticas: Molecular biology Endocrinology & metabolism Ciências biológicas ii Cell biology

Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 22128778

Direcció de correo del autor: sonia.fernandez@urv.cat oscar.yanes@urv.cat juanjose.vendrell@urv.cat

Identificador del autor: 0000-0003-2906-3788 0000-0003-3695-7157 0000-0002-6994-6115

Fecha de alta del registro: 2023-02-18

Versión del articulo depositado: info:eu-repo/semantics/publishedVersion

Enlace a la fuente original: https://www.sciencedirect.com/science/article/pii/S2212877815001969

URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/

Referencia al articulo segun fuente origial: Molecular Metabolism. 5 (1): 5-18

Referencia de l'ítem segons les normes APA: Ceperuelo-Mallafré V; Ejarque M; Serena C; Duran X; Montori-Grau M; Rodríguez MA; Yanes O; Núñez-Roa C; Roche K; Puthanveetil P; Garrido-Sánchez L; Sa (2016). Adipose tissue glycogen accumulation is associated with obesity-linked inflammation in humans. Molecular Metabolism, 5(1), 5-18. DOI: 10.1016/j.molmet.2015.10.001

DOI del artículo: 10.1016/j.molmet.2015.10.001

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2016

Tipo de publicación: Journal Publications