The doctoral dissertation in the field of Medicine 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?
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and is strongly associated with obesity and metabolic dysfunction. While simple liver steatosis is relatively benign, the development of inflammation and liver cell injury, termed metabolic dysfunction-associated steatohepatitis (MASH), increases the risk of liver fibrosis, cirrhosis, liver cancer, and cardiovascular disease. However, the metabolic alterations associated with MASH remain incompletely understood.
My doctoral research investigated these alterations by studying metabolites and fatty acids in the liver, blood, and adipose tissue of patients with steatosis and MASH. Understanding how metabolism differs between these tissues may provide new insights into the pathogenesis of MASH and support the development of better biomarkers for identifying patients at risk of progressive liver disease.
What are the key findings or observations of your doctoral research?
My doctoral research highlights that although MASLD is defined by changes in the liver, the associated metabolic alterations involve several tissues and are not uniform throughout the body. In the liver, MASH was associated with a distinct metabolite profile that was not similarly detectable in the circulation.
Fatty acid composition also differed between tissues. Polyunsaturated fatty acids were decreased in the liver of patients with MASH compared with those with steatosis, whereas in adipose tissue they were increased. These opposing changes suggest that fatty acid metabolism may be altered differently in the liver and adipose tissue in MASH. The fatty acid profile in blood appeared to reflect alterations in both tissues.
In addition, some circulating metabolic alterations were associated with cardiometabolic factors, such as hyperlipidemia, hyperglycemia and insulin resistance, rather than with liver histology alone. Together, these findings highlight that circulating metabolic profiles reflect both liver-related and systemic metabolic alterations. Therefore, studies based solely on blood samples provide only part of the picture of the metabolic processes associated with MASH and may not fully reflect what is occurring within the liver.
How can the results of your doctoral research be utilised in practice?
The results of this doctoral research provide new information on metabolic alterations associated with MASH and on how these alterations differ between the liver, circulation, and adipose tissue. They do not directly change the current diagnosis or treatment of MASLD, but provide hypotheses for future targeted studies.
MASLD is a heterogeneous disease, and different biological mechanisms may contribute to disease development and progression in different patients. As new treatments targeting different pathways become available, a deeper understanding of these mechanisms and biomarkers reflecting them may eventually help identify patients most likely to benefit from particular treatments.
The findings also highlight that metabolic alterations observed in blood may reflect contributions from several tissues and may not directly represent changes occurring in the liver. Future studies combining metabolic information from the liver and circulation may help identify which liver-related metabolic alterations can be reliably detected in blood. Ultimately, this could contribute to improved non-invasive assessment of MASLD and provide further insight into its pathophysiology.
What are the key research methods and materials used in your doctoral research?
The research was based on liver, blood, and adipose tissue samples from the well-characterized Kuopio Obesity Surgery Study (KOBS) cohort. The participants had undergone liver biopsy, allowing metabolic findings to be compared with detailed histological assessment of the liver. In one of the studies, findings were also evaluated in an independent external cohort from the University of Lille, France.
Non-targeted metabolomics was used to measure hundreds of metabolites in serum and liver tissue, while fatty acid composition was analyzed in liver, serum, and adipose tissue. In a subset of participants, liver RNA sequencing data were used to examine how metabolic findings were associated with gene expression. The molecular data were analyzed together with clinical characteristics, liver histology, and relevant genetic variants using statistical and bioinformatic methods.
The doctoral dissertation of Saana Palomurto, Lic Med, entitled Metabolomic profiling of metabolic dysfunction-associated steatotic liver disease, will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Lise Lotte Gluud of the University of Copenhagen, and the Custos will be Professor Ville Männistö of the University of Eastern Finland. The public examination will be held in English.
For further information, please contact:
Saana Palomurto, Lic Med, [email protected]
