• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

外周生物钟介导果蝇饮食限制依赖性的寿命和脂肪代谢变化。

Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila.

作者信息

Katewa Subhash D, Akagi Kazutaka, Bose Neelanjan, Rakshit Kuntol, Camarella Timothy, Zheng Xiangzhong, Hall David, Davis Sonnet, Nelson Christopher S, Brem Rachel B, Ramanathan Arvind, Sehgal Amita, Giebultowicz Jadwiga M, Kapahi Pankaj

机构信息

Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.

Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA.

出版信息

Cell Metab. 2016 Jan 12;23(1):143-54. doi: 10.1016/j.cmet.2015.10.014. Epub 2015 Nov 25.

DOI:10.1016/j.cmet.2015.10.014
PMID:26626459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4715572/
Abstract

Endogenous circadian clocks orchestrate several metabolic and signaling pathways that are known to modulate lifespan, suggesting clocks as potential targets for manipulation of metabolism and lifespan. We report here that the core circadian clock genes, timeless (tim) and period (per), are required for the metabolic and lifespan responses to DR in Drosophila. Consistent with the involvement of a circadian mechanism, DR enhances the amplitude of cycling of most circadian clock genes, including tim, in peripheral tissues. Mass-spectrometry-based lipidomic analysis suggests a role of tim in cycling of specific medium chain triglycerides under DR. Furthermore, overexpression of tim in peripheral tissues improves its oscillatory amplitude and extends lifespan under ad libitum conditions. Importantly, effects of tim on lifespan appear to be mediated through enhanced fat turnover. These findings identify a critical role for specific clock genes in modulating the effects of nutrient manipulation on fat metabolism and aging.

摘要

内源性生物钟协调着多种已知可调节寿命的代谢和信号通路，这表明生物钟是调节代谢和寿命的潜在靶点。我们在此报告，在果蝇中，核心生物钟基因 timeless（tim）和 period（per）是对饮食限制（DR）产生代谢和寿命反应所必需的。与昼夜节律机制的参与一致，DR增强了包括tim在内的大多数生物钟基因在周围组织中的循环振幅。基于质谱的脂质组学分析表明，tim在DR条件下特定中链甘油三酯的循环中发挥作用。此外，在外周组织中过表达tim可改善其振荡幅度，并在自由摄食条件下延长寿命。重要的是，tim对寿命的影响似乎是通过增强脂肪周转率来介导的。这些发现确定了特定生物钟基因在调节营养操纵对脂肪代谢和衰老的影响方面的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/07787ac70769/nihms734625f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/73a191b366c6/nihms734625f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/f4e42123f8c0/nihms734625f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/01e90a091ab6/nihms734625f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/5fa13129ae8d/nihms734625f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/7b218a3559ad/nihms734625f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/07787ac70769/nihms734625f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/73a191b366c6/nihms734625f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/f4e42123f8c0/nihms734625f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/01e90a091ab6/nihms734625f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/5fa13129ae8d/nihms734625f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/7b218a3559ad/nihms734625f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5e/4715572/07787ac70769/nihms734625f6.jpg

相似文献

1
Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila.外周生物钟介导果蝇饮食限制依赖性的寿命和脂肪代谢变化。
Cell Metab. 2016 Jan 12;23(1):143-54. doi: 10.1016/j.cmet.2015.10.014. Epub 2015 Nov 25.
2
Circadian clock genes' overexpression in Drosophila alters diet impact on lifespan.果蝇中生物钟基因的过表达改变了饮食对寿命的影响。
Biogerontology. 2019 Apr;20(2):159-170. doi: 10.1007/s10522-018-9784-2. Epub 2018 Nov 24.
3
Spliceosome factors target timeless () mRNA to control clock protein accumulation and circadian behavior in Drosophila.剪接体因子靶向 timeless()mRNA，以控制果蝇中的时钟蛋白积累和昼夜节律行为。
Elife. 2018 Dec 5;7:e39821. doi: 10.7554/eLife.39821.
4
Neuron-specific overexpression of core clock genes improves stress-resistance and extends lifespan of Drosophila melanogaster.神经元特异性过表达核心时钟基因可提高黑腹果蝇的应激抗性并延长其寿命。
Exp Gerontol. 2019 Mar;117:61-71. doi: 10.1016/j.exger.2018.11.005. Epub 2018 Nov 9.
5
Daily temperature cycles prolong lifespan and have sex-specific effects on peripheral clock gene expression in Drosophila melanogaster.日常温度循环延长寿命，并对黑腹果蝇外周时钟基因表达具有性别特异性影响。
J Exp Biol. 2021 May 15;224(10). doi: 10.1242/jeb.233213. Epub 2021 May 17.
6
Fluorescent Reporters for Studying Circadian Rhythms in Drosophila melanogaster.用于研究黑腹果蝇昼夜节律的荧光报告基因。
Methods Mol Biol. 2022;2482:353-371. doi: 10.1007/978-1-0716-2249-0_24.
7
Effect of spaceflight on the circadian rhythm, lifespan and gene expression of Drosophila melanogaster.太空飞行对黑腹果蝇昼夜节律、寿命和基因表达的影响。
PLoS One. 2015 Mar 23;10(3):e0121600. doi: 10.1371/journal.pone.0121600. eCollection 2015.
8
Circadian gene variants and the skeletal muscle circadian clock contribute to the evolutionary divergence in longevity across populations.昼夜节律基因变异和骨骼肌生物钟导致了不同种群之间寿命的进化差异。
Genome Res. 2019 Aug;29(8):1262-1276. doi: 10.1101/gr.246884.118. Epub 2019 Jun 27.
9
An RNAi Screen To Identify Protein Phosphatases That Function Within the Drosophila Circadian Clock.一项用于鉴定在果蝇生物钟中发挥作用的蛋白磷酸酶的RNA干扰筛选。
G3 (Bethesda). 2016 Dec 7;6(12):4227-4238. doi: 10.1534/g3.116.035345.
10
Achilles is a circadian clock-controlled gene that regulates immune function in Drosophila.阿克琉斯是一个生物钟控制的基因，调节果蝇的免疫功能。
Brain Behav Immun. 2017 Mar;61:127-136. doi: 10.1016/j.bbi.2016.11.012. Epub 2016 Nov 14.

引用本文的文献

1
Co-regulation of Nr1d1 and Pparα in age-related changes of lipid metabolism and its modulation by calorie restriction.Nr1d1和Pparα在脂质代谢年龄相关变化中的共同调节及其受卡路里限制的调控
Aging (Albany NY). 2025 Jul 28;17(7):1810-1833. doi: 10.18632/aging.206289.
2
Neuronal glycogen breakdown mitigates tauopathy via pentose-phosphate-pathway-mediated oxidative stress reduction.神经元糖原分解通过磷酸戊糖途径介导的氧化应激减轻来缓解tau蛋白病。
Nat Metab. 2025 Jun 30. doi: 10.1038/s42255-025-01314-w.
3
Neuronal Progenitors Suffer Genotoxic Stress in the Clock Mutant .

本文引用的文献

1
Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.中链甘油三酯改善高脂饮食诱导的肥胖小鼠的胰岛素抵抗和炎症。
Eur J Nutr. 2016 Apr;55(3):931-40. doi: 10.1007/s00394-015-0907-0. Epub 2015 Apr 25.
2
Lipidomic profiling of di- and tri-acylglycerol species in weight-controlled mice.体重控制小鼠中二酰基甘油和三酰基甘油种类的脂质组学分析。
PLoS One. 2015 Feb 23;10(2):e0116398. doi: 10.1371/journal.pone.0116398. eCollection 2015.
3
Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trials.
神经元祖细胞在生物钟突变体中遭受基因毒性应激。
Cells. 2024 Nov 23;13(23):1944. doi: 10.3390/cells13231944.
4
Systems biology approaches identify metabolic signatures of dietary lifespan and healthspan across species.系统生物学方法鉴定了跨物种的饮食寿命和健康跨度的代谢特征。
Nat Commun. 2024 Oct 29;15(1):9330. doi: 10.1038/s41467-024-52909-y.
5
A role for the circadian photoreceptor CRYPTOCHROME in regulating triglyceride metabolism in Drosophila.生物钟光受体 CRYPTOCHROME 在调控果蝇甘油三酯代谢中的作用。
G3 (Bethesda). 2024 Nov 6;14(11). doi: 10.1093/g3journal/jkae220.
6
Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions.热量限制的非典型代谢和分子作用是通过改变时间条件来揭示的。
Cell Rep. 2024 Sep 24;43(9):114663. doi: 10.1016/j.celrep.2024.114663. Epub 2024 Aug 20.
7
An Introductory Guide to Using Bloomington Drosophila Stock Center and FlyBase for Aging Research.使用 Bloomington 果蝇品系中心和 FlyBase 进行衰老研究的入门指南。
Cells. 2024 Jul 14;13(14):1192. doi: 10.3390/cells13141192.
8
Biological clock regulation by the gene family: a new perspective on tumor development.基因家族对生物钟的调控：肿瘤发展的新视角。
Front Cell Dev Biol. 2024 May 15;12:1332506. doi: 10.3389/fcell.2024.1332506. eCollection 2024.
9
Dietary restriction fails to extend lifespan of Drosophila model of Werner syndrome.饮食限制未能延长 Werner 综合征果蝇模型的寿命。
G3 (Bethesda). 2024 May 7;14(5). doi: 10.1093/g3journal/jkae056.
10
OXR1 maintains the retromer to delay brain aging under dietary restriction.OXR1 通过维持 retromer 来延缓饮食限制下的大脑衰老。
Nat Commun. 2024 Jan 11;15(1):467. doi: 10.1038/s41467-023-44343-3.
中链甘油三酯对体重减轻和身体成分的影响：随机对照试验的荟萃分析
J Acad Nutr Diet. 2015 Feb;115(2):249-263. doi: 10.1016/j.jand.2014.10.022.
4
Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism.SIRT6对昼夜节律转录进行分区，从而实现对细胞代谢的分离控制。
Cell. 2014 Jul 31;158(3):659-72. doi: 10.1016/j.cell.2014.06.050.
5
Insulin-FOXO3 signaling modulates circadian rhythms via regulation of clock transcription.胰岛素 - FOXO3信号通路通过调控生物钟转录来调节昼夜节律。
Curr Biol. 2014 Jun 2;24(11):1248-55. doi: 10.1016/j.cub.2014.04.018. Epub 2014 May 22.
6
The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice.在随意进食的小鼠中，常量营养素的比例而非热量摄入决定了心脏代谢健康、衰老和寿命。
Cell Metab. 2014 Mar 4;19(3):418-30. doi: 10.1016/j.cmet.2014.02.009.
7
PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan.PGRP-SC2 促进肠道免疫稳态，以限制共生失调并延长寿命。
Cell. 2014 Jan 16;156(1-2):109-22. doi: 10.1016/j.cell.2013.12.018.
8
Cryptochrome restores dampened circadian rhythms and promotes healthspan in aging Drosophila.CRY 恢复减弱的生物钟节律并促进衰老果蝇的健康寿命。
Aging Cell. 2013 Oct;12(5):752-62. doi: 10.1111/acel.12100. Epub 2013 Jun 25.
9
Molecular components of the Mammalian circadian clock.哺乳动物生物钟的分子组成部分。
Handb Exp Pharmacol. 2013(217):3-27. doi: 10.1007/978-3-642-25950-0_1.
10
Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease.中链甘油三酯可剂量依赖性地预防非酒精性脂肪性肝病大鼠模型中的肝病理变化。
Exp Biol Med (Maywood). 2013 Feb;238(2):151-62. doi: 10.1258/ebm.2012.012303.