Multi‐Tissue Multi‐Omics Nutrigenomics Indicates Context‐Specific Effects of Docosahexaenoic Acid on Rat Brain

Abstract

Scope: The influence of docosahexaenoic acid (DHA) on cardiometabolic and cognitive phenotypes, and multi-omic alterations in the brain under two metabolic conditions is explored to understand context-specific nutritional effects. Methods and results: Rats are randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduces serum triglyceride and improves insulin resistance and memory exclusively in the fructose-consuming rats. In hippocampus, DHA affects genes related to synapse functions in the chow group but immune functions in the fructose group; in hypothalamus, DHA alters immune pathways in the chow group but metabolic pathways in the fructose group. Network modeling reveals context-specific regulators of DHA effects, including Klf4 and Dusp1 for chow condition and Lum, Fn1, and Col1a1 for fructose condition in hippocampus, as well as Cyr61, JunB, Ier2, and Pitx2 under chow condition and Hcar1, Cdh1, and Osr1 under fructose condition in hypothalamus. Conclusion: DHA exhibits differential influence on epigenetic loci, genes, pathways, and metabolic and cognitive phenotypes under different dietary contexts, supporting population stratification in DHA studies to achieve precision nutrition.

Lipidomics Changes in a Murine Model of Neuropsychiatric Lupus

“…8 Numerous studies on lipidomics and neurological disorders have confirmed that lipid metabolism played an important role in brain lesions and mood disorders. 9,10 And peripheral metabolism changes can significantly affect the function of the brain. 9 Because of the important role of lipid metabolism in SLE and mood disorders, we considered the study of lipid metabolism in NPSLE mice.…”

“…9,10 And peripheral metabolism changes can significantly affect the function of the brain. 9 Because of the important role of lipid metabolism in SLE and mood disorders, we considered the study of lipid metabolism in NPSLE mice.…”