ChREBP plays a pivotal role in the nutrient-mediated regulation of metabolic gene expression in brown adipose tissue.
Life Sci
; 351: 122843, 2024 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-38880168
ABSTRACT
AIMS:
Carbohydrate-responsive element-binding protein (ChREBP) is a transcription factor that regulates several metabolic genes, including the lipogenic enzymes necessary for the metabolic conversion of carbohydrates into lipids. Although the crucial role of ChREBP in the liver, the primary site of de novo lipogenesis, has been studied, its functional role in adipose tissues, particularly brown adipose tissue (BAT), remains unclear. In this study, we investigated the role of ChREBP in BAT under conditions of a high-carbohydrate diet (HCD) and ketogenic diet (KD), represented by extremely low carbohydrate intake. MAINMETHODS:
Using an adeno-associated virus and Cas9 knock-in mice, we rapidly generated Chrebp brown adipocyte-specific knock-out (B-KO) mice, bypassing the necessity for prolonged breeding by using the Cre-Lox system. KEYFINDINGS:
We demonstrated that ChREBP is essential for glucose metabolism and lipogenic gene expression in BAT under HCD conditions in Chrebp B-KO mice. After nutrient intake, Chrebp B-KO attenuated the KD-induced expression of several inflammatory genes in BAT.SIGNIFICANCE:
Our results indicated that ChREBP, a nutrient-sensing regulator, is indispensable for expressing a diverse range of metabolic genes in BAT.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo Marrom
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Regulação da Expressão Gênica
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Camundongos Knockout
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
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Lipogênese
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article