AI Article Synopsis
- ChREBP is a transcription factor that plays a critical role in regulating metabolic genes, particularly those involved in converting carbohydrates to lipids, but its function in brown adipose tissue (BAT) under different diets is not well understood.
- The study utilized innovative genetic techniques to create brown adipocyte-specific knock-out mice to investigate ChREBP's role under high-carbohydrate and ketogenic diets.
- Findings revealed that ChREBP is crucial for glucose metabolism and the expression of lipogenic genes in BAT, especially under high-carbohydrate conditions, and also affects the inflammatory response in BAT during a ketogenic diet.
Article 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.
Main Methods: 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.
Key Findings: 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.
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| http://dx.doi.org/10.1016/j.lfs.2024.122843 | DOI Listing |
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