Comparing Soy and Milk Protein Regulation of Hepatic Omega-3 Fatty Acid Biosynthesis
- PMID: 40622084
- PMCID: PMC12232530
- DOI: 10.1096/fj.202501283R
Comparing Soy and Milk Protein Regulation of Hepatic Omega-3 Fatty Acid Biosynthesis
Abstract
The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have numerous benefits, including strong anti-inflammatory and triglyceride-lowering properties. EPA and DHA are primarily obtained by consuming fatty fish; however, they are also endogenously synthesized primarily in the liver from α-linolenic acid (ALA) through a pathway mediated by the delta-6 desaturase (D6D) enzyme. Previous reports in rodents and humans suggest that dietary proteins such as soy and dairy may impact this pathway differently. The primary aim was to investigate the effects of diets containing either soy or milk protein on the expression, abundance, and enzymatic activity of the desaturases and elongases regulating hepatic omega-3 fatty acid biosynthesis. Male C57BL/6N mice (n = 16 per group) were fed a moderate-fat diet for 8 weeks containing either 1% or 3% energy from ALA. Protein content (15% energy) corresponded to either skim milk powder (SMP) or soy protein isolate (SPI). Hepatic fatty acid content was quantified by gas chromatography-flame ionization detection. Gene expression and protein expression were assessed by RT-qPCR and western blotting, respectively. D6D activity was measured in isolated hepatic microsomes. Fat oxidation was examined using a high-resolution respirometer. Hepatic omega-3 fatty acids (ALA, SDA, EPA, DPAn-3) were lower in SPI-fed mice compared to SMP-fed mice. Fads1, Fads2, Elovl2, and Elovl5 expression was higher in SPI-fed mice compared to those fed SMP, while Srebp-1c expression was lower and Cpt1a expression higher in SPI-fed mice. Consistent with the changes seen at the gene expression levels, FADS2 protein abundance was higher in SPI-fed mice, whereas ELOVL5 protein expression was lower in the SPI groups. Little to no differences in microsomal D6D activity and mitochondrial respiration were detected. Our findings suggest that SPI-related reductions in hepatic omega-3 fatty acid content occur independent of changes in desaturase gene expression, protein expression, enzymatic activity, or mitochondrial respiration. Further studies investigating the influence of dietary proteins on ALA metabolism are therefore warranted.
Keywords: DHA; EPA; delta 6 desaturase; milk protein; omega‐3; soy protein.
© 2025 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
Conflict of interest statement
The authors declare no conflicts of interest.
Figures







References
-
- Calder P. C., “Omega‐3 Fatty Acids and Inflammatory Processes: From Molecules to Man,” Biochemical Society Transactions 45 (2017): 1105–1115. - PubMed
-
- Mozaffarian D. and Wu J. H. Y., “Omega‐3 Fatty Acids and Cardiovascular Disease: Effects on Risk Factors, Molecular Pathways, and Clinical Events,” Journal of the American College of Cardiology 58 (2011): 2047–2067. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials