A systems biology approach to study non-alcoholic fatty liver (NAFL) in women with obesity

Abraham S Meijnikman; Dimitra Lappa; Hilde Herrema; Omrum Aydin; Kimberly A Krautkramer; Valentina Tremaroli; Louise E Olofsson; Annika Lundqvist; Sjoerd Bruin; Yair Acherman; Joanne Verheij; Siv Hjorth; Victor E A Gerdes; Thue W Schwartz; Albert K Groen; Fredrik Bäckhed; Jens Nielsen; Max Nieuwdorp

doi:10.1016/j.isci.2022.104828

A systems biology approach to study non-alcoholic fatty liver (NAFL) in women with obesity

iScience. 2022 Aug 5;25(8):104828. doi: 10.1016/j.isci.2022.104828. eCollection 2022 Aug 19.

Authors

Abraham S Meijnikman^{1

2}, Dimitra Lappa³, Hilde Herrema¹, Omrum Aydin^{1

2}, Kimberly A Krautkramer⁴, Valentina Tremaroli⁴, Louise E Olofsson⁴, Annika Lundqvist⁴, Sjoerd Bruin², Yair Acherman², Joanne Verheij⁵, Siv Hjorth⁶, Victor E A Gerdes^{1

2}, Thue W Schwartz⁶, Albert K Groen¹, Fredrik Bäckhed^{4

7

8}, Jens Nielsen³, Max Nieuwdorp¹

Affiliations

¹ Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands.
² Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands.
³ Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
⁴ Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Department of Pathology, UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.
⁶ Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Heath and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁸ Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden.

Abstract

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.

Keywords: Biological sciences; Human metabolism; Physiology; Systems biology.