Charles Perkins Centre, University of Sydney, NSW 2006, Australia; Centre for Education and Research on Ageing, Concord RG Hospital, NSW 2139, Australia; ANZAC Research Institute, Sydney, NSW 2139, Australia.
Charles Perkins Centre, University of Sydney, NSW 2006, Australia.
Cell Metab. 2021 Dec 7;33(12):2367-2379.e4. doi: 10.1016/j.cmet.2021.10.016. Epub 2021 Nov 11.
Nutrient sensing pathways influence metabolic health and aging, offering the possibility that diet might be used therapeutically, alone or with drugs targeting these pathways. We used the Geometric Framework for Nutrition to study interactive and comparative effects of diet and drugs on the hepatic proteome in mice across 40 dietary treatments differing in macronutrient ratios, energy density, and drug treatment (metformin, rapamycin, resveratrol). There was a strong negative correlation between dietary energy and the spliceosome and a strong positive correlation between dietary protein and mitochondria, generating oxidative stress at high protein intake. Metformin, rapamycin, and resveratrol had lesser effects than and dampened responses to diet. Rapamycin and metformin reduced mitochondrial responses to dietary protein while the effects of carbohydrates and fat were downregulated by resveratrol. Dietary composition has a powerful impact on the hepatic proteome, not just on metabolic pathways but fundamental processes such as mitochondrial function and RNA splicing.
营养感应途径影响代谢健康和衰老，这使得饮食有可能成为一种治疗方法，无论是单独使用还是与针对这些途径的药物联合使用。我们使用营养的几何框架来研究饮食和药物对小鼠肝脏蛋白质组的相互作用和比较影响，这些小鼠接受了 40 种不同的饮食处理，包括宏量营养素比例、能量密度和药物治疗（二甲双胍、雷帕霉素、白藜芦醇）的差异。饮食能量与剪接体之间呈强烈负相关，而饮食蛋白质与线粒体之间呈强烈正相关，在高蛋白摄入时产生氧化应激。二甲双胍、雷帕霉素和白藜芦醇的作用小于饮食的作用，并抑制了对饮食的反应。雷帕霉素和二甲双胍降低了饮食蛋白对线粒体的反应，而白藜芦醇则下调了碳水化合物和脂肪的作用。饮食成分对肝脏蛋白质组有强大的影响，不仅对代谢途径有影响，而且对基本过程如线粒体功能和 RNA 剪接也有影响。
