Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/162037
Title: Low-density lipoprotein receptor-related protein 1 deficiency in cardiomyocytes reduces susceptibility to insulin resistance and obesity
Author: Benitez Amaro, Aleyda
Revuelta López, Elena
Bornachea, Olga
Cedó Giné, Lídia
Vea, Àngela
Herrero Rodríguez, Laura
Roglans i Ribas, Núria
Soler Botija, Carolina
Gonzalo Calvo, David de
Nasarre, Laura
Camino López, Sandra
García, Eduardo
Mato, Eugenia
Blanco Vaca, Francisco
Bayés Genís, Antoni
Sebastian, David
Laguna Egea, Juan Carlos
Serra i Cucurull, Dolors
Zorzano Olarte, Antonio
Escola Gil, Joan Carles
Llorente Cortés, Vicenta
Keywords: Insulina
Obesitat
Trastorns del metabolisme
Metabolisme dels lípids
Insulin
Obesity
Disorders of metabolism
Lipid metabolism
Issue Date: 26-Feb-2020
Publisher: W.B. Saunders
Abstract: Background: Low-density lipoprotein receptor-related protein 1 (LRP1) plays a key role in fatty acid metabolism and glucose homeostasis. In the context of dyslipemia, LRP1 is upregulated in the heart. Our aim was to evaluate the impact of cardiomyocyte LRP1 deficiency on high fat diet (HFD)-induced cardiac and metabolic alterations, and to explore the potential mechanisms involved. Methods: We used TnT-iCre transgenic mice with thoroughly tested suitability to delete genes exclusively in cardiomyocytes to generate an experimental mouse model with conditional Lrp1 deficiency in cardiomyocytes (TNT-iCre+-LRP1flox/flox). Findings: Mice with Lrp1-deficient cardiomyocytes (cm-Lrp1-/-) have a normal cardiac function combined with a favorable metabolic phenotype against HFD-induced glucose intolerance and obesity. Glucose intolerance protection was linked to higher hepatic fatty acid oxidation (FAO), lower liver steatosis and increased whole-body energy expenditure. Proteomic studies of the heart revealed decreased levels of cardiac pro-atrial natriuretic peptide (pro-ANP), which was parallel to higher ANP circulating levels. cm-Lrp1-/- mice showed ANP signaling activation that was linked to increased fatty acid (FA) uptake and increased AMPK/ ACC phosphorylation in the liver. Natriuretic peptide receptor A (NPR-A) antagonist completely abolished ANP signaling and metabolic protection in cm-Lrp1-/- mice. Conclusions: These results indicate that an ANP-dependent axis controlled by cardiac LRP1 levels modulates AMPK activity in the liver, energy homeostasis and whole-body metabolism.
Note: Versió postprint del document publicat a: https://doi.org/10.1016/j.metabol.2020.154191
It is part of: Metabolism-Clinical and Experimental, 2020, vol. 106, num. 154191
URI: http://hdl.handle.net/2445/162037
Related resource: https://doi.org/10.1016/j.metabol.2020.154191
ISSN: 0026-0495
Appears in Collections:Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Bioquímica i Fisiologia)

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