Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys.
Caloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys.
复制标题
DOI：
10.1016/j.cmet.2018.01.014
复制
发表时间：
2018-03-06
期刊：
影响因子：
29
通讯作者：
Anderson RM
中科院分区：
文献类型：
--
作者：
Rhoads TW;Burhans MS;Chen VB;Hutchins PD;Rush MJP;Clark JP;Stark JL;McIlwain SJ;Eghbalnia HR;Pavelec DM;Ong IM;Denu JM;Markley JL;Coon JJ;Colman RJ;Anderson RM
卡路里限制(CR)延长了不同物种的寿命并延缓了与年龄相关的疾病的发生。代谢调节通路参与了CR的发病机制，但其分子细节尚不清楚。在这里，我们展示了CR参与与高度集成的肝脏代谢重新编程相关的基因的RNA处理。我们对成年雄性恒河猴(Macaca Mulatta)在基线和对照或CR(30%限制)饮食2年后收集的肝活检进行了分子图谱分析。对来自肝脏转录组、蛋白质组和代谢组的20,000多个分子的定量研究表明，新陈代谢和RNA加工是CR反应的主要特征。预测模型确定了脂肪、支链氨基酸和短链碳代谢途径，CR网络中超过一半的基因使用了替代转录本。我们得出结论，基于RNA的机制是CR反应的中心，并且在代谢重编程中是不可或缺的。Rhoads等人。使用多平台高分辨率分子图谱来证明热量限制(CR)重新编程恒河猴的肝脏新陈代谢。他们确定了RNA处理在CR的机制中的作用，并表明CR代谢网络在RNA水平上受到实质性的调节。
Caloric Restriction (CR) extends lifespan and delays the onset of age-related disorders in diverse species. Metabolic regulatory pathways have been implicated in the mechanisms of CR, but the molecular details have not been elucidated. Here we show that CR engages RNA processing of genes associated with a highly integrated reprogramming of hepatic metabolism. We conducted molecular profiling of liver biopsies collected from adult male rhesus monkeys (Macaca mulatta) at baseline and after 2 years on control or CR (30% restricted) diet. Quantitation of over 20,000 molecules from the hepatic transcriptome, proteome, and metabolome, indicated that metabolism and RNA processing are major features of the response to CR. Predictive models identified lipid, branched chain amino acid, and short-chain carbon metabolic pathways, with alternate transcript use for over half of the genes in the CR network. We conclude that RNA-based mechanisms are central to the CR response and integral in metabolic reprogramming. Rhoads et al. use multi-platform high-resolution molecular profiling to demonstrate that caloric restriction (CR) reprograms hepatic metabolism in rhesus monkeys. They identify a role for RNA processing in the mechanisms of CR, and show that the CR metabolic network is subject to substantial regulation at the RNA level.
登录
查看更多内容
影响因子：
4
作者：
Bingol, Kerem;Li, Da-Wei;Bruschweiler-Li, Lei;Cabrera, Oscar A.;Megraw, Timothy;Zhang, Fengli;Brueschweiler, Rafael
通讯作者：
Brueschweiler, Rafael
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1126/science.1173635
发表时间：
2009-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Colman RJ;Anderson RM;Johnson SC;Kastman EK;Kosmatka KJ;Beasley TM;Allison DB;Cruzen C;Simmons HA;Kemnitz JW;Weindruch R
通讯作者：
Weindruch R
影响因子：
64.5
作者：
Fontana L;Partridge L
通讯作者：
Partridge L
影响因子：
23.9
作者：
Crews, Leslie A.;Balaian, Larisa;Delos Santos, Nathaniel P.;Leu, Heather S.;Court, Angela C.;Lazzari, Elisa;Sadarangani, Anil;Zipeto, Maria A.;La Clair, James J.;Villa, Reymundo;Kulidjian, Anna;Storb, Rainer;Morris, Sheldon R.;Ball, Edward D.;Burkart, Michael D.;Jamieson, Catriona H. M.
通讯作者：
Jamieson, Catriona H. M.