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2020-02-26

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cc-by-nc-nd (c) W.B. Saunders, 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/162037

Low-density lipoprotein receptor-related protein 1 deficiency in cardiomyocytes reduces susceptibility to insulin resistance and obesity

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https://doi.org/10.1016/j.metabol.2020.154191

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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.

Matèries

Insulina, Obesitat, Trastorns del metabolisme, Metabolisme dels lípids

Matèries (anglès)

Insulin, Obesity, Disorders of metabolism, Lipid metabolism

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Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citació

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, SEBASTIÁN MUÑOZ, David, LAGUNA EGEA, Juan carlos, SERRA I CUCURULL, Dolors, ZORZANO OLARTE, Antonio, ESCOLÀ GIL, Joan carles, LLORENTE CORTÉS, Vicenta. Low-density lipoprotein receptor-related protein 1 deficiency in cardiomyocytes reduces susceptibility to insulin resistance and obesity. _Metabolism-Clinical and Experimental_. 2020. Vol. 106, núm. 154191. [consulta: 24 de gener de 2026]. ISSN: 0026-0495. [Disponible a: https://hdl.handle.net/2445/162037]

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