Dietary macronutrients modulate the proteome of brown adipose tissue in males and their female offspring

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Abstract

Dietary macronutrient composition in males influences brown adipose tissue (BAT) size and BAT size of daughters in C57BL/6J mice. However, the effects of macronutrients and paternal effects on BAT function have yet to be characterized. We investigated the effects of macronutrient composition on the BAT proteome in male mice and offspring. In fathers, >50% of the proteome was affected by macronutrients. We identified two clusters with inverse patterns that correlated with BAT mass. Notably, uncoupling protein 1 (UCP1) was reduced on low-fat diets that promoted increased BAT mass, while there were increased levels of proteins involved in protein turnover. The same diets also led to a reduction in proteins involved in purine biosynthesis (purines are often UCP1 inhibitors). We also found that paternal protein intake negatively affected basigin expression in daughters, a protein that regulates Ucp1 transcription. Our results show that macronutrients in males remodel the protein expression of BAT directly and in their daughters.

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Macartney, E. L., Senior, A. M., Crean, A. J., Small, L., Ruffino, L., Pulpitel, T. J., … Simpson, S. J. (2025). Dietary macronutrients modulate the proteome of brown adipose tissue in males and their female offspring. Cell Reports, 44(8). https://doi.org/10.1016/j.celrep.2025.116050

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