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Lunges with dumbbells.

Doctoral defence of Susanne Csader, Dipl. Pharm., 6 Oct 2023: 12 weeks of HIIT ameliorated fatty liver disease

The doctoral dissertation in the field of Metabolic Diseases will be examined at the Faculty of Health Sciences at Kuopio campus. The public examination will be streamed online.

What is the topic of your doctoral research? Why is it important to study the topic?

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is a major public health concern. The prevalence of NAFLD has been increasing for decades, and is now the most common cause of chronic liver disease, affecting up to 32 % of the human population worldwide. Despite its high prevalence, no approved pharmaceutical therapy exists so far. Besides diet, the recommended treatment is increased physical activity. Several benefits of exercise have been shown, and the gut microbiome might mediate these benefits. However, the mechanisms and the taxonomic and functional bacterial signature behind the positive effects of exercise on NAFLD are poorly understood or not even elucidated yet. The ultimate goal of this doctoral thesis was to identify new metabolites associated with metabolic benefits of exercise in NAFLD. Moreover, this study aimed to elucidate the impact of exercise on gut microbiota as well as on adipose tissue gene expression.

What are the key findings or observations of your doctoral research?

12 weeks of HIIT without dietary changes and weight loss ameliorates NAFLD metabolic effects on a whole-body level. Alterations in amino acids in adipose tissue and lipid metabolism in plasma might play a crucial role in improved glucose metabolism. In addition, adipose tissue remodeling and changes in fat metabolism might be modified by exercise. . Despite unchanged diversity of the gut microbiota in NAFLD individuals during the intervention, significant modifications of the bacterial network were observed and could be linked to improvements in NAFLD. Overall, exercise training is beneficial at a whole-body level. However, to combat hepatic steatosis, exercise alone might not be enough, or another additional exercise regime should be considered, or one of a different type.

What are the key research methods and materials used in your doctoral research?

A 12-week randomized controlled intervention study was conducted without dietary changes and weight loss. While the control group kept their lifestyle unchanged, the intervention group performed supervised high-intensity interval training (HIIT) twice per week and one unsupervised light to moderate aerobic exercise session once per week. For metabolomic identification, non-targeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics analysis was used in adipose tissue (AT), plasma, urine, and stool. Shotgun metagenomics was performed, and differential correlation network and enrichment analysis were conducted to characterize the gut microbiota and associate them with clinical parameters. RNA sequencing of AT samples was conducted, and differential gene analysis and pathway analysis were executed to find alterations in gene expressions and pathways. Liquid chromatography quadruple time-of-flight mass tandem spectrometry (LC-QTOF-MS/MS) was used to detect differences in oxylipins.

The doctoral dissertation of Susanne Csader, Dipl. Pharm, entitled High-intensity interval training in nonalcoholic fatty liver disease:  Integrated metabolomic, metagenomic and transcriptomic approaches will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Emeritus Markku Savolainen of the University of Oulu, and the Custos will be Professor Ursula Schwab of the University of Eastern Finland.

Doctoral defence