The effect of Methionine Restriction using oxidized casein as protein source on the transcriptome of mouse livers

Ingestion of a diet with a restricted Methionine (MR) content results in robust activation of hepatic stress pathways regulated by PERK, ATF4, and Nfe2l2. In addition, genes regulating hepatic lipogenesis are downregulated. So far, data were obtained using a mix of elemental amino acids as the dietary protein source, which was replaced in this experiment with casein. To reduce methionine content, casein was oxidized and methionine was added back to a concentration similar to the diets using elemental amino acids as protein source. Results show that mice reduce body weight and adiposity on MR containing oxidized casein similar to MR containing elemental amino acids. Similarly, energy expenditure, as well as food and water intake were increased. The RNAseq experiment was conducted to compare the effect of MR using these two protein sources on the hepatic transcriptome. Overall design: Comparison of the effect of methionine restricted (MR) diet using either elemental amino acids (each 6 samples from Control and MR fed mice) or oxidized casein (each 6 samples from Control and MR fed mice) as protein sources on the hepatic transcriptome. The Control diets contain 0.86% methionine, the MR diets 0.17% methionine.