Sleeve-gastrectomy results in improved metabolism and a massive stress response of the liver proteome in a mouse model of metabolic dysfunction-associated steatohepatitis

Dr. med. Andreas Kroh 

Universitätsklinikum Aachen

Background: Bariatric surgery has been shown to improve the histopathological findings in patients with obesity and metabolic dysfunction-associated steatohepatitis, but there are also reports about non-responders or progressive disease after bariatric interventions. Therefore, it is of utmost importance to understand the pathophysiological processes in the liver after bariatric surgery.

Materials and methods: In the present study, 4 weeks old male C57/Bl6 mice were fed a Western Diet to induce metabolic dysfunction-associated steatohepatitis and sleeve-gastrectomy (SG), or sham operation in the pair-fed and ad libitum control group were performed. Mice were observed for two or eight weeks after surgery and metabolic assessment was performed throughout the experiment. Histopathology, flow cytometry and proteomic analyses were conducted to evaluate hepatic inflammation, liver metabolism and affected signaling pathways

Results: Weight loss was higher, and metabolism significantly improved after SG. Two weeks after SG major inflammatory and regulatory disturbances in the liver were observed. The proportion of hepatic CD3+ NK1.1+ cells were decreased, and proteins involved in apoptosis like Fas, Casp1 and Casp9 or in the acute phase response were upregulated in SG mice. These disturbances decreased in the long-term and we observed an increase of many proteins involved in lipid metabolism eight weeks following SG.

25.000 Euro (2016)