Food and Behaviour Research

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

Couteur D, Solon-Biet S, Parker B, Pulpitel T, Brandon A, Hunt N, Wali J, Gokarn R, Senior A, Cooney G, Raubenheimer D, Cogger V, James D, Simpson S (2021) Cell Metabolism doi: 10.1016/j.cmet.2021.10.016  

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  • Dietary energy intake has a negative correlation with abundance of spliceosome proteins
  • Protein intake correlates with abundance of mitochondrial proteins and oxidative stress
  • Metformin, rapamycin, and resveratrol dampen responses to nutrients
  • Abundance of SLC25A51, the mitochondrial NAD transporter, is increased with protein intake


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.