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HCBP6 诱导棕色脂肪组织激活和上调 BAT 细胞因子基因。

HCBP6-induced activation of brown adipose tissue and upregulated of BAT cytokines genes.

机构信息

Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China; Beijing Institute of Infectious Diseases, Beijing, 100015, China; National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China; Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.

Beijing Pan-Asia Tongze Institute of Biomedicine Co, Ltd., Beijing, 100103, China.

出版信息

J Therm Biol. 2022 Oct;109:103306. doi: 10.1016/j.jtherbio.2022.103306. Epub 2022 Aug 29.

Abstract

Brown adipose tissue is a thermogenic organ, which consumes chemical energy as heat to protect animals from low temperature and metabolic diseases. However, the role and mechanism of the new factor that up-regulates the heat-generating capacity of brown adipose tissue is still unclear. Here, we found that hepatitis C virus core binding protein 6 (HCBP6), as a key regulator gene in the homeostasis of liver lipid metabolism, is an important enhancer for activating brown fat to ensure thermogenesis. HCBP6 upregulates the expression of UCP1 and increases the number of mitochondria in brown adipocytes. In the BAT of HCBP6-knockout mice induced by a high-fat diet, UCP1 and BAT activity-related genes Pgc1α, Cidea and oxidation phosphorylation-related genes (OXPHOS) were significantly reduced. In addition, the transcriptomics results show that the loss of HCBP6 caused disorder of the metabolic pathway, the expression of brown adipocyte development genes was significantly reduced, and the expression of most BAT cytokine genes was reduced. In conclusion, HCBP6 increased ucp1-dependent thermogenesis in BAT and improved liver lipid metabolism, possibly by enhancing the activity of brown fat and changing the expression of BAT cytokine genes.

摘要

棕色脂肪组织是一种产热器官,它消耗化学能量产生热量,以保护动物免受低温和代谢疾病的影响。然而,上调棕色脂肪组织产热能力的新因子的作用和机制尚不清楚。在这里,我们发现丙型肝炎病毒核心结合蛋白 6(HCBP6)作为肝脏脂质代谢稳态的关键调节基因,是激活棕色脂肪以确保产热的重要增强子。HCBP6 上调 UCP1 的表达并增加棕色脂肪细胞中线粒体的数量。在高脂肪饮食诱导的 HCBP6 敲除小鼠的 BAT 中,UCP1 和与 BAT 活性相关的基因 Pgc1α、Cidea 和氧化磷酸化相关基因(OXPHOS)的表达显著降低。此外,转录组学结果表明,HCBP6 的缺失导致代谢途径紊乱,棕色脂肪细胞发育基因的表达显著降低,大多数 BAT 细胞因子基因的表达降低。总之,HCBP6 通过增加 BAT 中 ucp1 依赖性产热和改善肝脏脂质代谢来提高 UCP1 依赖性产热,这可能是通过增强棕色脂肪的活性和改变 BAT 细胞因子基因的表达来实现的。

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