Project description:INTRODUCTION: The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). APOE4 has reduced lipidation capacity and impaired lipid transport, disrupting neuronal maintenance. The high-density lipoprotein (HDL)-mimetic peptide 4F offers a potential therapeutic strategy. METHODS: To investigate how APOE4 alters brain gene expression and lipid metabolism and to evaluate the therapeutic potential of 4F, we performed dual-omics analysis in APOE4/4 (E4/4) and APOE3/3 (E3/3) mice treated intraperitoneally with D-enantiomer of 4F (D4F) or vehicle for 12 weeks to 13 months of age. RESULTS: APOE4/4 mice showed widespread transcriptomic and lipidomic alterations, including downregulation of lipid metabolism and synaptic pathways, increased ceramides, sphingomyelins, and cholesteryl esters, and decreased triglycerides and diglycerides. D4F treatment restored gene expression and lipid profiles toward APOE3/3 levels. DISCUSSION: These findings reveal molecular mechanisms underlying APOE4-driven dysregulation and support the therapeutic potential of HDL-mimetic peptides to mitigate APOE4-associated alterations in AD.
Project description:This project contains LC/MS-based metabolomic and lipidomic data generated from nucleus accumbens tissues following cocaine exposure
Project description:Oleaginous microalgae Nannochloropsis spp. are considered to be promissing species for production of biofuels and biomaterials. Nevertheless, its biofuel production remains to be economically unviable. Hence, further improvement of cultivation conditions and genetic traits for high-lipid contents without affecting growth is required. To understand genes involved in neutral lipid accumulation upon nitrogen deprivation (ND) in a novel isolate of Nannochloropsis sp. PJ12, we performed comparative transcriptomic and lipidomic analyses of cells under ND and NR (nitrogen replete) conditions. Transcriptomic profiling indicated that, while enzymes involved in TCA cycle in PJ12 under ND condition were upregulated compared to that under NR condition, those involved in Calvin cycle and glycolysis under ND condition were downregulated, consistent with the observation that quantum yield was reduced under ND condition. Furthermore, we showed that enzymes involved in fatty acid synthesis and glycerolipid synthesis were downregulated but not b-oxidation. Lipidomic profiling indicated that, while the level of neutral lipids in ND cells was increased compared to that of NR cells, level of photosynthetic membrane-lipids DGDG and MGDG was decreased. Taken together, our analysis indicated that TAG accumulation is attributed to the modification of membrane lipids derived primarily from “prokaryotic” pathway and secondarily from “eukaryotic” pathway based on the 16:X or 18:X fatty acid at the sn2 position of the glycerol backbone. We propose that two-phase (NR-ND) growth is ideal for biomass and biofuel production because ND reduces cell growth rate due to the loss of photosynthetic membrane and decreased quantum yield.
Project description:We investigate the underlying mechanism of the CP inhibition on F. prausnitzii by analysing its effects at the transcriptomic and lipidomic levels.
Project description:Transcriptional profiling of fetal, pediatric, and adult human intestinal enteroids following Human Coronavirus 229E infection at 32C and 37C.