二甲雙胍、白藜蘆醇和雷帕霉素抑制小鼠肝臟蛋白質(zhì)組的營(yíng)養(yǎng)性重編程

澳大利亞悉尼大學(xué)Stephen J. Simpson、David G. Le Couteur等研究人員合作發(fā)現(xiàn)，二甲雙胍、白藜蘆醇和雷帕霉素抑制小鼠肝臟蛋白質(zhì)組的營(yíng)養(yǎng)性重編程。該項(xiàng)研究成果于2021年11月11日在線發(fā)表在《細(xì)胞—代謝》雜志上。

研究人類(lèi)通過(guò)使用營(yíng)養(yǎng)幾何框架來(lái)揭示了飲食和藥物對(duì)小鼠肝臟蛋白質(zhì)組的互動(dòng)和比較效應(yīng)，這些飲食處理在宏量營(yíng)養(yǎng)素比例、能量密度和藥物處理（二甲雙胍、雷帕霉素、白藜蘆醇）方面有所不同。飲食能量和剪接體之間有強(qiáng)烈的負(fù)相關(guān)，飲食蛋白質(zhì)和線粒體之間有強(qiáng)烈的正相關(guān)，在高蛋白質(zhì)攝入時(shí)產(chǎn)生氧化壓力。

二甲雙胍、雷帕霉素和白藜蘆醇的作用小于并抑制了對(duì)飲食的反應(yīng)。雷帕霉素和二甲雙胍減少了線粒體對(duì)飲食蛋白質(zhì)的反應(yīng)，而碳水化合物和脂肪的影響被白藜蘆醇下調(diào)了。飲食成分對(duì)肝臟蛋白質(zhì)組有強(qiáng)大的影響，不僅對(duì)代謝途徑，而且對(duì)線粒體功能和RNA剪接等基本過(guò)程都有影響。

據(jù)介紹，營(yíng)養(yǎng)感應(yīng)途徑影響著新陳代謝的健康和衰老，并提供了飲食可能被單獨(dú)或與針對(duì)這些途徑的藥物一起用于治療的潛力。

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：《細(xì)胞—代謝》，創(chuàng)刊于2005年。隸屬于細(xì)胞出版社，最新IF：22.415

來(lái)源：Online