Adipose Tissue–Gut-Liver- Crosstalk in Metabolic Dysfunction–Associated Steatotic Liver Disease

• Applicants: Dr. Maximilian Krause, since 1/2026; Professor Dr. Kai Markus Schneider
• Subject Area: Gastroenterology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569298435

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30% of adults worldwide and includes various stages from steatosis to steatohepatitis, fibrosis and liver failure. The disease is closely linked to metabolic disorders such as obesity, impaired glucose metabolism and high blood pressure. In the development and progression of MASLD, there are complex interactions between the liver, intestine and adipose tissue, which are influenced by diet, lack of exercise and chronic stress. Adipose tissue can release both protective and pro-inflammatory mediators, which have a decisive influence on the course of MASLD. Despite numerous studies, the exact mechanisms of interaction between adipose tissue and liver are not sufficiently understood, particularly in the context of disease stage transitions (steatosis > steatohepatitis > fibrosis). Furthermore, the role of the different adipose tissue compartments (white vs. brown adipose tissue vs. immune cells) for the pathophysiology in the different stages is unclear. Based on published data and our own preliminary work, this project puts forward the overarching hypothesis that impaired adipose tissue function plays a central role in the development and progression of MASLD. We hypothesize that altered lipid storage capacity, increased secretion of inflammatory cytokines (particularly IL-6) and dysregulated adipokine signaling in adipose tissue act as central drivers of liver inflammation, systemic glucose intolerance and gut barrier dysfunction, all of which contribute to the onset and progression of MASLD. The project is based on a translational approach integrating both human cohorts as well as functional in-vivo and in-vitro experiments and incorporating state-of-the-art techniques in hepatology, genomics and bioinformatics. In the study of the adipose-liver-gut axis, we have defined three specific sub-objectives that will be addressed in a corresponding work package (WP). WP1: Investigation of the interactions between adipose tissue, liver and intestine in the course of the course of MASLD by means of multi-omic characterisation in human cohorts. WP2: Investigation of the function of adipose tissue using experimental models to validate findings from human studies and to clarify mechanistic relationships. WP3: Investigate the role of IL-6 as a key adipose tissue-derived cytokine that promotes inflammation, impairs the intestinal barrier and damages the liver. A better understanding of the interplay between adipose tissue, liver and intestine in MASLD development and progression could lead to new therapeutic approaches to prevent disease progression.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Andreas Dahl, until 1/2026