Cytosolic nucleic acid sensing and mitochondrial transcriptomic changes as early triggers of metabolic disease in db/db mice.

Autor: Ludwig-Słomczyńska AH; Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland. agnieszka.ludwig@uj.edu.pl., Seweryn MT; Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland.; Biobank Lab, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland., Wiater J; Department of Histology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland., Borys A; Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland., Ledwoń A; Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland., Druszczyńska M; Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland., Łabieniec-Watała M; Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland., Lis GJ; Department of Histology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland., Wołkow PP; Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland. pawel.wolkow@uj.edu.pl.
Jazyk: angličtina
Zdroj: Mammalian genome : official journal of the International Mammalian Genome Society [Mamm Genome] 2024 Mar; Vol. 35 (1), pp. 68-76. Date of Electronic Publication: 2023 Nov 18.
DOI: 10.1007/s00335-023-10026-z
Abstrakt: Animal models of diabetes, such as db/db mice, are a useful tool for deciphering the genetic background of molecular changes at the initial stages of disease development. Our goal was to find early transcriptomic changes in three tissues involved in metabolism regulation in db/db mice: adipose tissue, muscle tissue and liver tissue. Nine animals (three per time point) were studied. Tissues were collected at 8, 12 and 16 weeks of age. Transcriptome-wide analysis was performed using mRNA-seq. Libraries were sequenced on NextSeq (Illumina). Differential expression (DE) analysis was performed with edgeR. The analysis of the gene expression profile shared by all three tissues revealed eight upregulated genes (Irf7, Sp100, Neb, Stat2, Oas2, Rtp4, H2-T24 and Oasl2) as early as between 8 and 12 weeks of age. The most pronounced differences were found in liver tissue: nine DE genes between 8 and 12 weeks of age (Irf7, Ly6a, Ly6g6d, H2-Dma, Pld4, Ly86, Fcer1g, Ly6e and Idi1) and five between 12 and 16 weeks of age (Irf7, Plac8, Ifi44, Xaf1 and Ly6a) (adj. p-value < 0.05). The mitochondrial transcriptomic profile also changed with time: we found two downregulated genes in mice between 8 and 12 weeks old (Ckmt2 and Cox6a2) and five DE genes between 12 and 16 weeks of age (Mavs, Tomm40L, Mtfp1, Ckmt2 and Cox6a2). The KEGG pathway analysis showed significant enrichment in pathways related to the autoimmune response and cytosolic DNA sensing. Our results suggest an important involvement of the immunological response, mainly cytosolic nucleic acid sensing, and mitochondrial signalling in the early stages of diabetes and obesity.
(© 2023. The Author(s).)
Databáze: MEDLINE
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