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肝特异性 Bmal1 基因敲除小鼠的代谢特征及脂代谢表型

Metabolic Profile and Lipid Metabolism Phenotype in Mice with Conditional Deletion of Hepatic BMAL1.

机构信息

School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China.

Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou 310053, China.

出版信息

Int J Mol Sci. 2024 May 31;25(11):6070. doi: 10.3390/ijms25116070.

Abstract

The disruption of circadian rhythms (CRs) has been linked to metabolic disorders, yet the role of hepatic BMAL1, a key circadian regulator, in the whole-body metabolism and the associated lipid metabolic phenotype in the liver remains unclear. floxed () and hepatocyte-specific knockout () C57BL/6J mice underwent a regular feeding regimen. Hepatic CR, lipid content, mitochondrial function, and systemic metabolism were assessed at zeitgeber time (ZT) 0 and ZT12. Relevant molecules were examined to elucidate the metabolic phenotype. Hepatocyte-specific knockout of disrupted the expression of rhythmic genes in the liver. mice exhibited decreased hepatic TG content at ZT0, primarily due to enhanced lipolysis, reduced lipogenesis, and diminished lipid uptake. The β-oxidation function of liver mitochondria decreased at both ZT0 and ZT12. Our findings on the metabolic profile and associated hepatic lipid metabolism in the absence of in hepatocytes provides new insights into metabolic syndromes from the perspective of liver CR disturbances.

摘要

昼夜节律(CRs)的破坏与代谢紊乱有关,但肝生物钟关键调节因子 BMAL1 在全身代谢和肝脏相关脂质代谢表型中的作用仍不清楚。 floxed () 和肝细胞特异性 knockout () C57BL/6J 小鼠接受了常规喂养方案。在 Zeitgeber 时间(ZT)0 和 ZT12 时评估肝 CR、脂质含量、线粒体功能和全身代谢。检查相关分子以阐明代谢表型。肝细胞特异性 knockout of 破坏了肝脏中节律基因的表达。 小鼠在 ZT0 时表现出肝 TG 含量降低,主要是由于脂肪分解增强、脂肪生成减少和脂质摄取减少。肝线粒体的β-氧化功能在 ZT0 和 ZT12 时均降低。我们在肝细胞中缺乏 时对代谢特征和相关肝脂质代谢的研究结果,从肝 CR 紊乱的角度为代谢综合征提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb0/11172555/32728f0b8bc6/ijms-25-06070-g001.jpg

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