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慢性睡眠限制对雄性小鼠白色脂肪组织中转录沉默调节蛋白1信号调控的影响

Effects of Chronic Sleep Restriction on Transcriptional Sirtuin 1 Signaling Regulation in Male Mice White Adipose Tissue.

作者信息

Rendine Marco, Cocci Paolo, de Vivo Luisa, Bellesi Michele, Palermo Francesco Alessandro

机构信息

School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.

Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, 20133 Milan, Italy.

出版信息

Curr Issues Mol Biol. 2024 Mar 7;46(3):2144-2154. doi: 10.3390/cimb46030138.

Abstract

Chronic sleep restriction (CSR) is a prevalent issue in modern society that is associated with several pathological states, ranging from neuropsychiatric to metabolic diseases. Despite its known impact on metabolism, the specific effects of CSR on the molecular mechanisms involved in maintaining metabolic homeostasis at the level of white adipose tissue (WAT) remain poorly understood. Therefore, this study aimed to investigate the influence of CSR on sirtuin 1 (SIRT1) and the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway in the WAT of young male mice. Both genes interact with specific targets involved in multiple metabolic processes, including adipocyte differentiation, browning, and lipid metabolism. The quantitative PCR (qPCR) results demonstrated a significant upregulation of SIRT-1 and some of its target genes associated with the transcriptional regulation of lipid homeostasis (i.e., PPARα, PPARγ, PGC-1α, and SREBF) and adipose tissue development (i.e., leptin, adiponectin) in CSR mice. On the contrary, DNA-binding transcription factors (i.e., CEBP-β and C-myc), which play a pivotal function during the adipogenesis process, were found to be down-regulated. Our results also suggest that the induction of SIRT1-dependent molecular pathways prevents weight gain. Overall, these findings offer new, valuable insights into the molecular adaptations of WAT to CSR, in order to support increased energy demand due to sleep loss.

摘要

慢性睡眠限制(CSR)是现代社会中一个普遍存在的问题,它与多种病理状态相关,从神经精神疾病到代谢性疾病。尽管已知其对新陈代谢有影响,但CSR对白色脂肪组织(WAT)维持代谢稳态所涉及的分子机制的具体影响仍知之甚少。因此,本研究旨在探讨CSR对年轻雄性小鼠WAT中沉默调节蛋白1(SIRT1)和过氧化物酶体增殖物激活受体γ(PPARγ)信号通路的影响。这两个基因都与多个代谢过程中涉及的特定靶点相互作用,包括脂肪细胞分化、褐变和脂质代谢。定量PCR(qPCR)结果表明,CSR小鼠中SIRT-1及其一些与脂质稳态转录调控相关的靶基因(即PPARα、PPARγ、PGC-1α和SREBF)以及脂肪组织发育相关基因(即瘦素、脂联素)显著上调。相反,在脂肪生成过程中起关键作用的DNA结合转录因子(即CEBP-β和C-myc)被发现下调。我们的结果还表明,SIRT1依赖性分子途径的诱导可防止体重增加。总体而言,这些发现为WAT对CSR的分子适应性提供了新的、有价值的见解,以支持因睡眠不足而增加的能量需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac11/10969409/0f71e5611a42/cimb-46-00138-g001.jpg

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