A systems biology approach to study non-alcoholic fatty liver (NAFL) in women with obesity
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Non-alcoholic fatty liver disease (NAFLD) is now the most frequent global chronic liver disease. Individuals with NAFLD exhibited an increased risk of all-cause mortality driven by extrahepatic cancers and liver and cardiovascular disease. Once the disease is established, women have a higher risk of disease progression and worse outcome. It is therefore critical to deepen the current knowledge on the pathophysiology of NAFLD in women. Here, we used a systems biology approach to investigate the contribution of different organs to this disease. We analyzed transcriptomics profiles of liver and adipose tissues, fecal metagenomes, and plasma metabolomes of 55 women with and without NAFLD. We observed differences in metabolites, expression of human genes, and gut microbial features between the groups and revealed that there is substantial crosstalk between these different omics sets. Multi-omics analysis of individuals with NAFLD may provide novel strategies to study the pathophysiology of NAFLD in humans.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 104828 |
| Tidsskrift | iScience |
| Vol/bind | 25 |
| Udgave nummer | 8 |
| Antal sider | 18 |
| ISSN | 2589-0042 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
The BARIA study is funded by the Novo Nordisk Foundation (NNF15OC0016798). The Novo Nordisk Foundation Center for Basic Metabolic Research is supported by an unconditional grant (NNF10CC1016515) from the Novo Nordisk Foundation to University of Copenhagen. The BARIA study is a Scandinavian-Dutch collaboration. Funding from Knut and Alice Wallenberg Foundation is also acknowledged. The computations and RNA Sequencing were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at C3SE (SNIC Computational Center of Chalmers University of Technology) partially funded by the Swedish Research Council through grant agreement no. 2018-05973. We thank Torsten Scheithauer for making the figures. T.W.S. M.N. J.N. and F.B. supervised this work; A.S.M. and D.L. conducted conceptual design, data curation, data analysis, visualization and main manuscript preparation; A.S.M. O.A. S.B. M.L.D.B, collected medical data and biopsies; J.V. and D.L.P.P. reviewed all liver biopsies; V.T. and A.L. performed DNA, RNA, and metabolomics isolations and optimizations; L.M.O. conducted metagenomics data analysis; L.E.O. F.B. and J.N. coordinated project administration; D.L. A.S.M. H.H. K.K. L.M.O. Ö.A. Y.I.Z.A. M.L.D.B. V.T. L.E.O. A.L. S.H. V.E.A.G. A.K.G. T.W.S. M.N. F.B. and J.N. conducted hypothesis generation, manuscript review and editing. The authors declare no conflict of interest.
Funding Information:
The BARIA study is funded by the Novo Nordisk Foundation ( NNF15OC0016798 ). The Novo Nordisk Foundation Center for Basic Metabolic Research is supported by an unconditional grant ( NNF10CC1016515 ) from the Novo Nordisk Foundation to University of Copenhagen . The BARIA study is a Scandinavian-Dutch collaboration. Funding from Knut and Alice Wallenberg Foundation is also acknowledged. The computations and RNA Sequencing were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at C3SE (SNIC Computational Center of Chalmers University of Technology) partially funded by the Swedish Research Council through grant agreement no. 2018-05973 . We thank Torsten Scheithauer for making the figures.
Publisher Copyright:
© 2022 The Author(s)
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