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Single-cell gene expression profiles of pancreatic islets from two β-cell specific knockout mouse models (βZKO-Mip and βZKO-Rip), along with RIP-Cre and MIP-Cre mice, were analyzed after being fed a high-fat diet (HFD).

ABSTRACT: The islet is composed of diverse cell types that work together to regulate its endocrine function. To investigate this, we performed comparative single-cell RNA sequencing (scRNA-seq) on islets from 16-week-old βZKO-Mip, βZKO-Rip, RIP-Cre, and MIP-Cre mice, all of which were fed a high-fat diet (HFD) from 12 to 16 weeks. Sequencing was carried out using the Chromium Next GEM Single Cell 3' Reagent Kits. Each islet sample was derived from at least three mice with the same genotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE288211 | GEO | 2025/09/22

REPOSITORIES: GEO

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Project description:To explore the underlying mechanism for the regulatory role of branched-chain amino acids (BCAA) catabolism in hypothalamic RIP-Cre neurons to metabolic organs under normal chow diet feeding, we established RIP-Cre neurons selective BCAA catabolic enzyme branched-chain ketoacid dehydrogenase E1 subunit alpha(Bckdha) knockout mice, we conducted RNA sequencing on the inguinal adipose tissue (iWAT), epididymal adipose tissues (eWAT), and liverfrom wild type (WT, Bckdhaf/f) and knockout (KO, Bckdhaf/f;RIP-Cre) mice (two groups in total). Three biological replicates were performed for each group. Methods: RNA sequencing (RNA-Seq) and data analysis were performed by Gene Denovo Biotechnology (Guangzhou, China). Results: In comparison with findings in the Bckdhaf/f group, 393 up-regulated and 214 down-regulated differentially expressed genes (DEGs) were identified in eWAT from Bckdhaf/f;RIP-Cre group . Similarly, 41 up-regulated genes and 152 down-regulated DEGs were identified in iWAT from Bckdhaf/f;RIP-Cre compared to the Bckdhaf/f group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEGs in eWAT were enriched in the categories including all subclass pathways in carbohydrate metabolism class, insulin resistance, PPAR signaling, oxidative phosphorylation, thermogenesis, carbon metabolism, fatty acid metabolism, biosynthesis of amino acids and degenerative disease pathways. Similarly, DEGs in iWATwere clustered in the pathways, including the TCA cycle, pyruvate metabolism, glucagon signaling, glycolysis and gluconeogenesis, and carbon metabolism. These changes indicated broad disturbance in WAT energy metabolism in Bckdhaf/f;RIP-Cre mice. Liver transcriptomes showed minor perturbances in subclasses in lipid metabolism, advanced glycation end products and their receptor (AGE-RAGE), PPAR, estrogen, prolactin signaling pathways. Notably, all 13 mitochondrial DNA encoded mRNA were all significantly down-regulated in eWAT of Bckdhaf/f;RIP-Cre mice, along with nucleus DNA encoded mitochondrial located mRNA. Conclusions: Our results using RNA-Seq indicated universal defects of mitochondrial gene expression in eWAT and iWAT.

Dataset Information

Single-cell gene expression profiles of pancreatic islets from two β-cell specific knockout mouse models (βZKO-Mip and βZKO-Rip), along with RIP-Cre and MIP-Cre mice, were analyzed after being fed a high-fat diet (HFD).

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