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二甲双胍、白藜芦醇和雷帕霉素抑制小鼠肝脏蛋白质组的营养性重编程

更新时间:2021-11-25点击次数:2661

澳大利亚悉尼大学Stephen J. Simpson、David G. Le Couteur等研究人员合作发现,二甲双胍、白藜芦醇和雷帕霉素抑制小鼠肝脏蛋白质组的营养性重编程。该项研究成果于2021年11月11日在线发表在《细胞—代谢》杂志上。


研究人类通过使用营养几何框架来揭示了饮食和药物对小鼠肝脏蛋白质组的互动和比较效应,这些饮食处理在宏量营养素比例、能量密度和药物处理(二甲双胍、雷帕霉素、白藜芦醇)方面有所不同。饮食能量和剪接体之间有强烈的负相关,饮食蛋白质和线粒体之间有强烈的正相关,在高蛋白质摄入时产生氧化压力。


二甲双胍、雷帕霉素和白藜芦醇的作用小于并抑制了对饮食的反应。雷帕霉素和二甲双胍减少了线粒体对饮食蛋白质的反应,而碳水化合物和脂肪的影响被白藜芦醇下调了。饮食成分对肝脏蛋白质组有强大的影响,不仅对代谢途径,而且对线粒体功能和RNA剪接等基本过程都有影响。


据介绍,营养感应途径影响着新陈代谢的健康和衰老,并提供了饮食可能被单独或与针对这些途径的药物一起用于治疗的潜力。


附:英文原文

Title: Nutritional reprogramming of mouse liver proteome is dampened by metformin, resveratrol, and rapamycin

Author: David G. Le Couteur, Samantha M. Solon-Biet, Benjamin L. Parker, Tamara Pulpitel, Amanda E. Brandon, Nicholas J. Hunt, Jibran A. Wali, Rahul Gokarn, Alistair M. Senior, Gregory J. Cooney, David Raubenheimer, Victoria C. Cogger, David E. James, Stephen J. Simpson

Issue&Volume: 2021-11-11

Abstract: Nutrient sensing pathways influence metabolic health and aging, offering the possibilitythat diet might be used therapeutically, alone or with drugs targeting these pathways.We used the Geometric Framework for Nutrition to study interactive and comparativeeffects of diet and drugs on the hepatic proteome in mice across 40 dietary treatmentsdiffering in macronutrient ratios, energy density, and drug treatment (metformin,rapamycin, resveratrol). There was a strong negative correlation between dietary energyand the spliceosome and a strong positive correlation between dietary protein andmitochondria, generating oxidative stress at high protein intake. Metformin, rapamycin,and resveratrol had lesser effects than and dampened responses to diet. Rapamycinand metformin reduced mitochondrial responses to dietary protein while the effectsof carbohydrates and fat were downregulated by resveratrol. Dietary composition hasa powerful impact on the hepatic proteome, not just on metabolic pathways but fundamentalprocesses such as mitochondrial function and RNA splicing.

DOI: 10.1016/j.cmet.2021.10.016



期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415




来源:Online