Transcriptomic Analysis of the Effects of a Fish Oil Enriched Diet on Murine Brains

Abstract

The health benefits of fish oil enriched with high omega-3 polyunsaturated fatty acids (n-3 PUFA) are widely documented. Fish oil as dietary supplements, however, show moderate clinical efficacy, highlighting an immediate scope of systematic in vitro feedback. Our transcriptomic study was designed to investigate the genomic shift of murine brains fed on fish oil enriched diets. A customized fish oil enriched diet (FD) and standard lab diet (SD) were separately administered to two randomly chosen populations of C57BL/6J mice from their weaning age until late adolescence. Statistical analysis mined 1,142 genes of interest (GOI) differentially altered in the hemibrains collected from the FD- and SD-fed mice at the age of five months. The majority of identified GOI (∼40%) encodes proteins located in the plasma membrane, suggesting that fish oil primarily facilitated the membrane-oriented biofunctions. FD potentially augmented the nervous system's development and functions by selectively stimulating the Src-mediated calcium-induced growth cascade and the downstream PI3K-AKT-PKC pathways. FD reduced the amyloidal burden, attenuated oxidative stress, and assisted in somatostatin activation—the signatures of attenuation of Alzheimer's disease, Parkinson's disease, and affective disorder. FD induced elevation of FKBP5 and suppression of BDNF, which are often linked with the improvement of anxiety disorder, depression, and post-traumatic stress disorder. Hence we anticipate efficacy of FD in treating illnesses such as depression that are typically triggered by the hypoactivities of dopaminergic, adrenergic, cholinergic, and GABAergic networks. Contrastingly, FD's efficacy could be compromised in treating illnesses such as bipolar disorder and schizophrenia, which are triggered by hyperactivities of the same set of neuromodulators. A more comprehensive investigation is recommended to elucidate the implications of fish oil on disease pathomechanisms, and the result-driven repositioning of fish oil utilization may revitalize its therapeutic efficacy.

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

“…Low dose bryostatin-1 is currently being used in phase II clinical trials for the treatment of AD. Omega-3 polyunsaturated fatty acids reduce PKC mediated oxidative stress in a transgenic Aβ model [154]. Yessotoxin, a PKC activator, also decreases both hyperphosphorylated tau and Aβ accumulation [10].…”

Multi-tissue Multi-omics Nutrigenomics Indicates Context-specific Effects of DHA on Rat Brain

“…Between the two dietary conditions (chow vs. fructose) and between tissues, we also identified a consistent set of pathways affected by DHA, including ECM-receptor interaction, Focal adhesion, and PI3K-Akt signaling. These pathways act in or through plasma membrane, which was revealed to be the location of proteins encoded by the majority of genes affected by a fish oil enriched diet [32] . ECM, once known as a pure scaffold to support surrounding cells, is being recognized as an important regulator in neural development, such as proliferation, differentiation, morphogenesis, neuronal migration, formation of axonal process, the myelin sheath, and synapse [33] .…”

Differences in omega‐3 and omega‐6 polyunsaturated fatty acid consumption in people at ultra‐high risk of psychosis, first‐episode schizophrenia, and in healthy controls

“…n-3 PUFAs are known to influence gene expression by modulating a number of transcription factors, such as nuclear factor-κB (NF-κB), peroxisome proliferatoractivated receptors (PPAR), retinoid X receptors (RxR) and sterol regulatory element-binding protein 1c (SREBP-1c). 54 These transcription factors are involved in the regulation of processes implicated in the pathophysiology of schizophrenia, such as neuroinflammation (NF-κB), fatty acid metabolism (SREBP-1c), neuronal development, differentiation and myelination (PPAR) and the vitamin A signalling pathway (RxR). [55][56][57][58] n-6/n-3 ratio has been shown to influence gene expression via regulation of PPARs, functioning as transcription factors related to cellular development, myelination of neurons and lipid homeostasis.…”