Low-density lipoprotein receptor-related protein 1 deficiency in cardiomyocytes reduces susceptibility to insulin resistance and obesity.
Adenylate Kinase
/ metabolism
Animals
Atrial Natriuretic Factor
/ metabolism
Cells, Cultured
Diet, High-Fat
Glucose Intolerance
/ genetics
Insulin Resistance
/ genetics
Lipid Metabolism
/ genetics
Low Density Lipoprotein Receptor-Related Protein-1
/ deficiency
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Mice, Transgenic
Myocytes, Cardiac
/ metabolism
Obesity
/ genetics
AMPK
ANP
Cardiomyocyte
Fatty acid oxidation
Heart
Liver
Lrp1
Journal
Metabolism: clinical and experimental
ISSN: 1532-8600
Titre abrégé: Metabolism
Pays: United States
ID NLM: 0375267
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
22
08
2019
revised:
14
02
2020
accepted:
24
02
2020
pubmed:
1
3
2020
medline:
7
7
2020
entrez:
1
3
2020
Statut:
ppublish
Résumé
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. 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 Mice with Lrp1-deficient cardiomyocytes (cm-Lrp1 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.
Sections du résumé
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
FINDINGS
Mice with Lrp1-deficient cardiomyocytes (cm-Lrp1
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.
Identifiants
pubmed: 32112822
pii: S0026-0495(20)30055-X
doi: 10.1016/j.metabol.2020.154191
pii:
doi:
Substances chimiques
Low Density Lipoprotein Receptor-Related Protein-1
0
Lrp1 protein, mouse
0
Atrial Natriuretic Factor
85637-73-6
Adenylate Kinase
EC 2.7.4.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
154191Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have declared no potential conflicts of interest.