二甲雙胍、白藜蘆醇和雷帕霉素抑制小鼠肝臟蛋白質組的營養性重編程

澳大利亞悉尼大學Stephen J. Simpson、David G. Le Couteur等研究人員合作發現，二甲雙胍、白藜蘆醇和雷帕霉素抑制小鼠肝臟蛋白質組的營養性重編程。該項研究成果于2021年11月11日在線發表在《細胞—代謝》雜志上。

研究人類通過使用營養幾何框架來揭示了飲食和藥物對小鼠肝臟蛋白質組的互動和比較效應，這些飲食處理在宏量營養素比例、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烈的負相關，飲食蛋白質和線粒體之間有強烈的正相關，在高蛋白質攝入時產生氧化壓力。

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

據介紹，營養感應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或與針對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：《細胞—代謝》，創刊于2005年。隸屬于細胞出版社，最新IF：22.415

來源：Online