Identification of regulatory networks and crosstalk factors in brown adipose tissue and liver of a cold-exposed cardiometabolic mouse model.
Cardiovasc Diabetol
; 23(1): 298, 2024 Aug 14.
Article
em En
| MEDLINE
| ID: mdl-39143620
ABSTRACT
BACKGROUND:
Activation of brown adipose tissue (BAT) has gained attention due to its ability to dissipate energy and counteract cardiometabolic diseases (CMDs).METHODS:
This study investigated the consequences of cold exposure on the BAT and liver proteomes of an established CMD mouse model based on LDL receptor-deficient (LdlrKO) mice fed a high-fat, high-sucrose, high-cholesterol diet for 16 weeks. We analyzed energy metabolism in vivo and performed untargeted proteomics on BAT and liver of LdlrKO mice maintained at 22 °C or 5 °C for 7 days.RESULTS:
We identified several dysregulated pathways, miRNAs, and transcription factors in BAT and liver of cold-exposed Ldlrko mice that have not been previously described in this context. Networks of regulatory interactions based on shared downstream targets and analysis of ligand-receptor pairs identified fibrinogen alpha chain (FGA) and fibronectin 1 (FN1) as potential crosstalk factors between BAT and liver in response to cold exposure. Importantly, genetic variations in the genes encoding FGA and FN1 have been associated with cardiometabolic-related phenotypes and traits in humans.DISCUSSION:
This study describes the key factors, pathways, and regulatory networks involved in the crosstalk between BAT and the liver in a cold-exposed CMD mouse model. These findings may provide a basis for future studies aimed at testing whether molecular mediators, as well as regulatory and signaling mechanisms involved in tissue adaption upon cold exposure, could represent a target in cardiometabolic disorders.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo Marrom
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Receptores de LDL
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Transdução de Sinais
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Temperatura Baixa
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Camundongos Knockout
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Proteômica
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Modelos Animais de Doenças
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Metabolismo Energético
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Redes Reguladoras de Genes
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Fígado
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article