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
Affiliations
Abraham S. Meijnikman
Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands; Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands; Corresponding author
Dimitra Lappa
Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
Hilde Herrema
Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands
Omrum Aydin
Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands; Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands
Kimberly A. Krautkramer
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Valentina Tremaroli
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Louise E. Olofsson
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Annika Lundqvist
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Sjoerd Bruin
Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands
Yair Acherman
Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands
Joanne Verheij
Department of Pathology, UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
Siv Hjorth
Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Victor E.A. Gerdes
Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands; Department of Surgery, Spaarne Hospital, Hoofddorp, the Netherlands
Thue W. Schwartz
Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Albert K. Groen
Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands
Fredrik Bäckhed
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Heath and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg, Sweden
Jens Nielsen
Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Corresponding author
Max Nieuwdorp
Departments of Internal and Experimental Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands; Corresponding author
Summary: 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.
