Faster DPAn-3 turnover in heart, perirenal adipose tissue and red blood cells in males compared to female mice fed an ALA- or EPA-only diet

Females have higher DHA levels than males, potentially due to differences in DHA synthesis and turnover rates from n-3 PUFA precursors. Here, we use compound specific isotope analysis to determine sex differences in n-3 PUFA turnover rates in C57BL/6N allocated to 12-week dietary interventions of either ALA, EPA or DHA. Each diet regimen fed low carbon-13 (δ13C)-n-3 PUFA diet for 4 weeks, followed by a high δ13C-n-3 PUFA diet for 8 weeks (n=4 per diet, time point, sex). Fatty acid levels and δ13C were measured in blood and tissues post-diet switch, and tissue turnover rates determined. EPA-fed females had higher DHA, while males had higher EPA and DPAn-3 in heart, perirenal adipose tissue, and red blood cells (RBCs). Heart DHA turnover from dietary ALA was 28.1% faster in females than males (p=0.045) and 25.9% faster from dietary EPA (p=0.027). Conversely, males had 35.8% faster heart DPAn-3 turnover rates from dietary EPA (p=0.012) and 86.5% faster rates from dietary ALA (p=0.0005). DPAn-3 turnover in males was 113% (p=0.0012) and 102% (p=0.0045) faster in adipose and 266% (p=0.0007) and 93.5% (p=0.0082) faster in RBCs from dietary ALA (p=0.0012) and EPA (p=0.0045), respectively, compared to females. These findings align with published liver data, where fatty acid synthesis primarily occurs, suggesting females may compensate with increased synthesis and turnover downstream of DPAn-3. The tissue-wide sex differences in DPAn-3 synthesis and turnover necessitates further investigation into DHA synthesis/turnover from dietary DPAn-3 to better elucidate mechanisms contributing to sex differences in DHA levels.