Overweight and obesity are the primary risk factors for developing the most common chronic liver disease, metabolic dysfunction-associated steatotic liver disease. When fat accumulates in the liver (steatosis), it can disrupt normal cellular function, leading to inflammation and the deposition of connective tissue, known as fibrosis. In some cases, this fibrosis progresses to irreversible scarring, resulting in liver cirrhosis. Cirrhosis can have potentially fatal outcomes, including liver-related complications and hepatocellular carcinoma.
The molecular mechanisms driving why only certain individuals with liver fat deposits progress to advanced liver disease remain unclear. Additionally, there is a lack of blood-based biomarkers for diagnosing steatotic liver disease. Current blood markers can only exclude advanced steatotic liver disease through calculation algorithms. Intermediate or elevated results require further investigation, including elastography (using magnetic resonance imaging or FibroScan) to evaluate liver fat percentage and stiffness, and possibly a liver biopsy.
We conduct several prospective studies on steatotic liver disease and cirrhosis, aiming to identify blood-based biomarkers. Using mass spectrometry, NMR, and antibody-based techniques, we seek circulating molecules that can indicate the degree of liver fat and fibrosis. Through both "untargeted" and "targeted" proteomics and metabolomics, we hope to find markers that will improve and simplify the diagnosis and prognosis of chronic liver disease.
To better understand molecular mechanisms in the liver, we have established an ex vivo model system for metabolic flux analysis. We cultivate thin slices of liver tissue and supply them with nutrients labeled with stable isotopes. Using mass spectrometry, we measure the isotope ratios and levels of various molecules within the tissue. These experimental data, combined with mathematical modeling then allow us to calculate nutrient flow and enzymatic activity in liver tissue.
