Multi-omics characterization of a diet-induced obese model of non-alcoholic steatohepatitis

Helene M Ægidius, Sanne S Veidal, Michael Feigh, Philip Hallenborg, Michele Puglia, Tune H Pers, Niels Vrang, Jacob Jelsing, Birgitte R Kornum, Blagoy Blagoev, Kristoffer T G Rigbolt

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Abstract

To improve the understanding of the complex biological processes underlying the development of non-alcoholic steatohepatitis (NASH), a multi-omics approach combining bulk RNA-sequencing based transcriptomics, quantitative proteomics and single-cell RNA-sequencing was used to characterize tissue biopsies from histologically validated diet-induced obese (DIO) NASH mice compared to chow-fed controls. Bulk RNA-sequencing and proteomics showed a clear distinction between phenotypes and a good correspondence between mRNA and protein level regulations, apart from specific regulatory events discovered by each technology. Transcriptomics-based gene set enrichment analysis revealed changes associated with key clinical manifestations of NASH, including impaired lipid metabolism, increased extracellular matrix formation/remodeling and pro-inflammatory responses, whereas proteomics-based gene set enrichment analysis pinpointed metabolic pathway perturbations. Integration with single-cell RNA-sequencing data identified key regulated cell types involved in development of NASH demonstrating the cellular heterogeneity and complexity of NASH pathogenesis.

Original languageEnglish
Article number1148
JournalScientific Reports
Volume10
Issue number1
Number of pages12
ISSN2045-2322
DOIs
Publication statusPublished - 2020

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