The Dietary Protein Source Modulates Obesity Development and Induces Distinct Plasma Lipid Profiles and Transcriptome...

Diets based on dairy or seafood proteins are reported to be less obesogenic than diets based on terrestrial meat proteins. The metabolic pathways underlying these differences, including processes related to thermogenesis, remain incompletely understood. Here, we investigated responses at levels of the transcriptome and the metabolome associated with potentially obesogenic high-fat, high-protein diets using casein, cod, or chicken as protein sources in mice kept at thermoneutral conditions or room temperature to evaluate metabolic responses to different housing temperatures. By performing plasma metabolomics analyses combined with RNA sequencing and gene set enrichment analyses of liver, muscle, white- and brown adipose tissue, we aimed to decipher the metabolic output and pathways modulated by intake of different dietary proteins. Dietary protein intake of casein, cod, or chicken led to differences in obesity development independent of housing temperature. The diet-specific phenotype was associated with a distinct plasma lipid profile and transcriptomic profile in liver and adipose tissue. One-carbon metabolism emerged as a potentially affected key pathway, and the mechanistic target of rapamycin complex 1/2 appeared as a predicted upstream regulator and accordingly suggested to be associated with protein source-dependent differences in obesity development and related metabolic disturbances.