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Father’s Protein Intake Determines Daughters’ “Metabolic Physique”?

 Uncategorized    Thursday, 2025/11/13

This study found in C57BL/6J mice that male dietary macronutrients affect over 50% of the brown adipose tissue (BAT) proteome and negatively regulate the expression of basement membrane proteoglycan in daughters’ BAT, providing a basis for dietary intervention in metabolic health.

Fig1. Graphical abstract

Fig1. Graphical abstract

Modern individuals increasingly focus on the relationship between diet and health, from weight management to the prevention of metabolic diseases, with dietary details closely linked to bodily functions. Brown adipose tissue (BAT), as a key organ in regulating energy expenditure and maintaining metabolic homeostasis, is a focal point in the study of how diet influences this process and whether it is transmitted to offspring through paternal lineage.

Recently, a study published in Cell Reports titled “Dietary macronutrients modulate the proteome of brown adipose tissue in males and their female offspring” systematically explored how male dietary macronutrients (proteins, carbohydrates, fats) regulate the BAT proteome in both themselves and their female offspring.

The study involved male C57BL/6J mice (F0 generation, fathers) who were provided with ten diets with consistent caloric content but varying macronutrient proportions. Results showed that F0 males on a low-fat diet (particularly moderate protein, high carbohydrate combination) experienced the highest weight gain and significant increases in both subcutaneous white adipose tissue (WAT) and interscapular BAT weight. On a low-protein diet, increased food intake demonstrated the protein leverage effect.

Fig2. Surface plots of F0 male food intake, F0 male weight gain, F0 male WAT weight, F0 male BAT weight, as well as F1 female offspring WAT weight and F1 female offspring BAT weight across the 10 diets

Fig2. Surface plots of F0 male food intake, F0 male weight gain, F0 male WAT weight, F0 male BAT weight, as well as F1 female offspring WAT weight and F1 female offspring BAT weight across the 10 diets

Analysis of the F0 males’ BAT proteome identified 2,582 proteins, with 1,385 significantly affected by diet and classified into five protein clusters with different nutritional response patterns. Clusters 3 and 4 exhibited opposite expression patterns and both were related to BAT weight: Cluster 3 proteins (including uncoupling protein 1 UCP1 and creatine kinase BCKB ) showed high expression under high-fat diets (low carb, low protein), enriched in purine synthesis and metabolism; Cluster 4 proteins (including proteasomal subunits PSMB2, PSMC5, PSMD4, and valosin-containing protein VCP ) showed high expression under low-fat diets, involved in ubiquitin-dependent protein degradation. The expression trend of Cluster 4 proteins corresponded with BAT weight in F0 males, while Cluster 3 showed an opposite correlation—UCP1, as a key protein in BAT non-shivering thermogenesis, showed expression negatively correlated with BAT weight. High BAT weight under low-fat diets but low UCP1 expression suggested non-UCP1 dependent thermogenic mechanisms. Additionally, the high expression of proteasomal proteins in Cluster 4 under low-fat diets might maintain protein homeostasis under cellular stress in BAT, while changes in purine synthesis-related proteins in Cluster 3 might affect UCP1 activity by modulating its inhibitors (purine compounds).

Related Proteins

Cat.No. # Product Name Source (Host) Species Tag Protein Length Price
UCP1-27R Recombinant Rat UCP1 protein, His-tagged E.coli Rat His 179-296 a.a.
UCP1-28R Recombinant Rat UCP1 protein, His/GST-tagged E.coli Rat GST&His 179-296 a.a.
UCP1-9176H Recombinant Human UCP1, His-tagged E.coli Human His 96-185a.a.
Ucp1-281M Recombinant Mouse Ucp1 Protein, His-tagged E.coli Mouse His Pro179~Leu296
Ucp1-283R Recombinant Rat Ucp1 Protein, His/GST-tagged E.coli Rat GST&His Pro179~Leu296
UCP1-2916H Recombinant Human UCP1 protein, His-tagged E.coli Human His 1-307 aa
CKB-11263H Recombinant Human CKB, GST-tagged E.coli Human GST 1-381a.a.
CKB-2729H Recombinant Human Creatine Kinase, Brain, His-tagged E.coli Human His
CKB-495H Recombinant Human CKB protein, His-tagged Insect Cells Human His 2-281 a.a.
PSMB2-1321H Recombinant Human Proteasome (prosome, macropain) Subunit, Beta Type, 2, His-tagged E.coli Human His
PSMB2-30366TH Recombinant Human PSMB2, His-tagged E.coli Human His Full L. 1-201 a.a.
PSMC5-3184H Recombinant Human PSMC5 protein, His-tagged E.coli Human His 1-406 aa
PSMC5-1080Z Recombinant Zebrafish PSMC5 Mammalian Cells Zebrafish His
PSMD4-2031H Recombinant Human PSMD4, His-tagged E.coli Human His 1-377aa
PSMD4-1810H Recombinant Human PSMD4 protein, GST-tagged E.coli Human GST 1-377 aa
PSMD4-422H Recombinant Human PSMD4 Protein, His/GST-tagged E.coli Human GST&His Met1~Lys377
VCP-3656H Recombinant Human VCP protein, GST-tagged E.coli Human GST 345-644 aa

In terms of transgenerational effects, analysis of F1 female (daughters) and male (sons) offspring BAT proteomes showed that paternal diet only affected the daughters’ BAT proteome: the expression of basement membrane glycoprotein (BSG) in daughters’ BAT negatively correlated with paternal dietary protein proportion—the more protein the father consumed, the lower the BSG expression in the daughters’ BAT. BSG is a known key protein regulating UCP1 transcription and normal BAT function, suggesting that paternal diet might indirectly regulate daughters’ metabolic function by affecting BSG expression in BAT. No detectable effect of paternal diet was found on sons’ BAT proteome, indicating a distinctly gender-specific transgenerational effect.

Fig3. Schematic networks of the significant proteins that were involved in enriched biological processes

Fig3. Schematic networks of the significant proteins that were involved in enriched biological processes

This study is the first to systematically analyze, at the proteome level, the regulatory effects of male dietary macronutrients on BAT function in themselves and their offspring, revealing specific patterns of dietary influence on BAT protein expression (such as the inverse relationship of UCP1 with BAT weight and the critical role of protein turnover) and discovering specific transgenerational effects on female offspring. These findings provide a new perspective for understanding the relationship between diet and metabolic health, and suggest that optimizing men’s dietary structure might not only improve their own metabolism but also potentially protect their daughters’ metabolic health. This lays the foundation for future exploration of the molecular mechanisms in transgenerational metabolic regulation (such as BSG pathways) and the development of targeted dietary intervention strategies, holding significant theoretical and practical implications for the prevention and management of metabolic diseases.

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Reference

  1. Macartney EL, Senior AM, Crean AJ, et al. Dietary macronutrients modulate the proteome of brown adipose tissue in males and their female offspring. Cell Rep. 2025;44(8):116050. doi:10.1016/j.celrep.2025.116050

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