Omega‑3 Fatty Acids Responsive Proteins and Reduction in Breast Density in Obese Postmenopausal Women

We reported that breast density (BD)
was inversely correlated with
the plasma level of DHA in postmenopausal obese, but not in nonobese,
women given Lovaza (n-3FA). To identify protein biomarkers for the
possible differential effect of n-3FA on BD between obese and nonobese
women, an iTRAQ method was performed to analyze plasma from obese
and lean women at each time point (baseline, 12 and 24-months, n = 10 per group); 173 proteins with >95% confidence
(Unuses
Score >1.3 and local false discovery rate estimation <5%) were identified.
Comparative analysis between various groups identified several differentially
expressed proteins (hemopexin precursor, vitamin D binding protein
isoform 1 precursor [VDBP], fibronectin isoform 10 precursor [FN],
and α-2 macroglobulin precursor [A2M]). Western blot analysis
was performed to verify the differential expression of proteins in
the iTRAQ study, and those found to be altered in a tumor protective
fashion by an n-3FA rich diet in our previous preclinical study; gelsolin,
VDBP, and FN were altered by n-3FA in a manner consistent with reduction
in inflammation in obese women. To test the impact of our findings
on breast cancer risk reduction by n-3FA, a posthoc analysis revealed
that n-3FA administration reduced BD selectively in obese postmenopausal
women.