TREM2 sustains macrophage-hepatocyte metabolic coordination in NAFLD and sepsis [Mouse_Kupffer_cell_RNA_seq]

The goals of this study are to explore the potential mechanism underlying fatty acid oxidation defects in high fat diet (HFD)-fed Trem2-/- livers, we performed RNA-seq and profiled Kupffer cells (KCs) transcriptomes isolated from 8-week HFD-fed Trem2-/- mice and WT littermates. Gene ontology (GO) analysis revealed that antigen processing and presentation, mitochondrial oxidative phosphorylation and ATP synthesis were impaired in Trem2-/- KCs. However, gene links to chemotaxis (Ccr2, Cx3cr1, Spp1), cytokine secretion (Cd36, Acsl1, Mmp19) were upregulated in Trem2-/- KCs. Interestingly, positively regulated genes in RNA polymerase II-mediated pri-miRNA transcription (Bmp2, Klf4) and exsomes (Exos) secretion (Cd63, Cd9) were enriched in Trem2-/- KCs. 8-weeks old Trem2-deficient (Trem2–/–) and littermate wild-type (WT) mice were placed on 8 weeks High fat diet feeding, and then their livers Kupffer cells (KCs) were harvest for KCs transcriptome analysis.