Sa1940 ENDOSCOPIC SLEEVE GASTROPLASTY IMPROVES NONALCOHOLIC FATTY LIVER DISEASE–RELATED LIVER DAMAGE IN YORKSHIRE PIGS BY RESHAPING CELLULAR INTERACTIONS AND HEPATIC ADIPOCYTOKINE PRODUCTION

Abstract

To investigate whether the modulation of local cellular cross-talks and the modification of hepatic adipocytokine expression could mechanistically explain the improvement of liver histopathology after Endoscopic Sleeve Gastroplasty (ESG) in Yorkshire Pigs with nonalcoholic fatty liver disease (NAFLD). Fifteen male Yorkshire pigs with similar weight were selected in separate compartments and fed with high-fat diets. After 8 weeks of feeding, they were randomly divided into a control group, a sham operation group, and an ESG group. Yorkshire pigs in the ESG group underwent ESG and York pigs in the sham operation group underwent sham surgery. Gastroscopy and upper gastrointestinal angiography were reviewed at 4 weeks, 8 weeks, and 12 weeks after surgery to confirm the success of ESG. York pigs were sacrificed at 12 weeks after surgery, blood samples were collected, and serum TG, TC, and free fatty acids were measured by ELISA. The liver shape of York pigs was observed, liver tissues were taken, and HE staining was performed. Hepatic progenitor cells, hepatic stellate cells (HSCs), macrophages, and adipocytokines were evaluated by immunohistochemistry and immunofluorescence. Compared with the sham operation group, liver biopsy samples demonstrated a significant improvement of NAFLD Activity Score and fibrosis. Immunohistochemistry indicated a significant reduction of hepatocyte cell cycle arrest, ductular reaction, activated HSC, and macrophage number compared with the sham operation group. The activation state of HSC was accompanied by modification in the expression of the autophagy marker LC3. Hepatocyte expression of adiponectin from ESG was significant higher than the sham operation group. Moreover, ESG caused decreased resistin expression in Sox9+ hepatic progenitor cells compared with the sham operation group. The number of S100A9+ macrophages was also reduced by ESG correlating with resistin expression. Finally, serum levels of proinflammatory cytokines significantly correlated with macrophages and activated HSC numbers. The histologic improvement induced by ESG is associated with the reduced activation of local cellular compartments (hepatic progenitor cells, HSCs, and macrophages), thus, strengthening the role of cellular interactions and hepatic adipocytokine production in the pathogenesis of NAFLD.