Sleeve-gastrectomy results in improved metabolism and a massive stress response of the liver proteome in a mouse model of metabolic dysfunction-associated steatohepatitis
Andreas Kroh,
Sophia Schmitz,
Saskia Köhne,
Julia Andruszkow,
Jochen Nolting,
Christian Preisinger,
Karsten Große,
Roman M. Eickhoff,
Daniel Heise,
Thorsten Cramer,
Karl Peter Rheinwalt,
Patrick Hamid Alizai,
Ulf Peter Neumann,
Tom Florian Ulmer
Affiliations
Andreas Kroh
General-, Visceral-, Pediatric and Transplant Surgery, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany; Corresponding author.
Sophia Schmitz
General-, Visceral-, Pediatric and Transplant Surgery, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany; General-, Visceral- and Transplant Surgery, Uniklinik Essen, Hufelandstr. 55, 45147, Essen, Germany
Saskia Köhne
General-, Visceral-, Pediatric and Transplant Surgery, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany
Julia Andruszkow
Institute of Pathology, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany
Jochen Nolting
General-, Visceral-, Pediatric and Transplant Surgery, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany
Christian Preisinger
Proteomics Facility, Interdisciplinary Center for Clinical Research (IZKF) Aachen, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany
Karsten Große
Department of Medicine III, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074 Aachen, Germany
Roman M. Eickhoff
General-, Visceral-, Pediatric and Transplant Surgery, RWTH Aachen University Hospital, Pauwelsstr. 30, 52074, Aachen, Germany
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. Conclusions: The rapid weight loss and decrease of hepatic fat after SG lead to a proinflammatory response in the liver in the early phase after surgery, which changes to a more moderate immune response in the long-term. We suggest a preoperative risk stratification and postoperative surveillance depending on the histopathological findings.
