Contribution of Poly-unsaturated Fatty Acids on Cerebral Neurobiology: An Integrated Omics Approach with Epigenomic Focus [Agilent]

Fish oil or its major constituent, namely omega-3 poly-unsaturated fatty acid (n3-PUFA), are popular diets to improve neurogenesis, neuroprotection, and overall brain functions. A growing number of studies advocate for the balanced dietary supplements of n3- and n6-PUFA to maximize the brain functions. Our objective was to probe the implication of PUFA to ameliorate social stress (SS). Mice were fed a customized n-3 PUFA-enriched diet (ERD, n3:n6= 7:1), a balanced diet (BLD, n3:n6= 1:1) or a standard lab diet (STD, n3:n6= 1:6). Past reports linked these diets to brain transcriptomic regulations; hence, we aimed to investigate the effects of these diets on mice exposed to Aggressor-exposed SS (Agg-E SS) model. Mice randomly encountered life-threatening trauma from conspecific aggressor for 10 consecutive days. Stressed mice on STD showed multiple behavioral deficits that lingered even 6 weeks post-Agg-E SS. In comparison, ERD and BLD elevated bodyweights but potentially triggered behavioral resilience to SS. Comprehensive mapping of the behavioral traits projected a diet-specific variance, which was mirrored by the brain transcriptomic readouts. We focused on those brain transcriptomic networks that were exclusively perturbed by the cumulative effects of Diet, Stress and Time. STD adversely affected the gene networks associated with the cell mortality, energy homeostasis and neurodevelopment disorder; however, BLD showed long-term benefits in regulating these gene networks. Further titration of PUFA supplements in daily diets can reduce the adverse effects caused by unbalanced supplement of PUFA without compromising their health benefits. A N-3 PUFA-enriched diet (ERD, n3:n6= 7:1) and a balanced diet (BLD, n3:n6= 1:1) were customized to contain equivalent caloric content as that of the standard lab diet (STD, n3:n6= 1:6). These diets were administered to three groups of C57BL/6j male mice from their weaning age until late adolescence. Left hemibrains were analyzed for differential transcripts, DNA methylation and microRNAs.