Sleeve-Gastrectomy results in improved metabolism and a massive stress response of the liver proteome in a mouse model of nonalcoholic steatohepatitis

Introduction: Bariatric surgery has been shown to improve the histopathological findings in patients with obesity and non-alcoholic steatohepatitis, but there are also reports about non-responder or progressive disease after bariatric interventions. Therefore, it is of utmost importance to understand the pathophysiological processes in the liver after bariatric surgery. Material and Methods: In the present study, mice were fed a Western Diet to induce non-alcoholic steatohepatitis and sleeve-gastrectomy (SG), or sham operation was performed. Mice were observed for two or eight weeks after surgery and metabolic assessment was performed throughout the experiment. Histopathology, fluorescence associated cell sorting and proteomic analysis 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, but these disturbances decreased in the long-term. Conclusion: 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.