Emily J Onufer1, Yong-Hyun Han2, Rafael S Czepielewski2, Cathleen M Courtney1, Stephanie Sutton1, Gwendalyn J Randolph2, Brad W Warner3. 1. Division of Pediatric Surgery, Department of Surgery, St. Louis Children's Hospital, Washington University in St. Louis School of Medicine, St. Louis, MO. 2. Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO. 3. Division of Pediatric Surgery, Department of Surgery, St. Louis Children's Hospital, Washington University in St. Louis School of Medicine, St. Louis, MO. Electronic address: brad.warner@wustl.edu.
Abstract
BACKGROUND: The optimal regimen for enteral nutritional support in the management of children with short bowel syndrome (SBS) is not well characterized. A high fat, enteral diet is theoretically beneficial due to increased caloric density and enhanced structural adaptation. We therefore sought to determine the long-term effects of a high fat diet (HFD) on liver injury, a common complication of SBS, compared to a standard chow (SC) diet. METHODS: Using a parenteral nutrition-independent model of resection-associated liver injury, C57BL/6 mice underwent a sham operation or a 50% or 75% proximal small bowel resection (SBR). Mice in each group were then fed either a HFD (35% kcal fat) or SC (13% kcal fat). At post-operative week 15, markers of liver injury were quantified. RESULTS: Liver triglyceride levels were increased from 7- to 19-fold in mice on the HFD compared to mice fed SC in the sham, 50%, and 75% resection groups. Serum ALT (2.2-fold increase in 75% resected mice compared to sham controls) and AST (2.0- and 2.7-fold increases in 50% and 75% resected mice, respectively) levels as well as fibrotic liver staining were elevated only in resected mice fed a HFD. CONCLUSION: Long-term enteral feeding of HFD in our murine SBS model is associated with hepatic steatosis and liver injury. Our observation that liver steatosis and injury occur independent of parenteral nutrition suggests that enteral feeding composition and magnitude of intestinal loss may make a significant contribution to intestinal failure-associated liver disease.
BACKGROUND: The optimal regimen for enteral nutritional support in the management of children with short bowel syndrome (SBS) is not well characterized. A high fat, enteral diet is theoretically beneficial due to increased caloric density and enhanced structural adaptation. We therefore sought to determine the long-term effects of a high fat diet (HFD) on liver injury, a common complication of SBS, compared to a standard chow (SC) diet. METHODS: Using a parenteral nutrition-independent model of resection-associated liver injury, C57BL/6 mice underwent a sham operation or a 50% or 75% proximal small bowel resection (SBR). Mice in each group were then fed either a HFD (35% kcal fat) or SC (13% kcal fat). At post-operative week 15, markers of liver injury were quantified. RESULTS: Liver triglyceride levels were increased from 7- to 19-fold in mice on the HFD compared to mice fed SC in the sham, 50%, and 75% resection groups. Serum ALT (2.2-fold increase in 75% resected mice compared to sham controls) and AST (2.0- and 2.7-fold increases in 50% and 75% resected mice, respectively) levels as well as fibrotic liver staining were elevated only in resected mice fed a HFD. CONCLUSION: Long-term enteral feeding of HFD in our murine SBS model is associated with hepatic steatosis and liver injury. Our observation that liver steatosis and injury occur independent of parenteral nutrition suggests that enteral feeding composition and magnitude of intestinal loss may make a significant contribution to intestinal failure-associated liver disease.
Authors: Elizabeth P Newberry; Yan Xie; Susan Kennedy; Xianlin Han; Kimberly K Buhman; Jianyang Luo; Richard W Gross; Nicholas O Davidson Journal: J Biol Chem Date: 2003-10-08 Impact factor: 5.157
Authors: Yong-Hyun Han; Emily J Onufer; Li-Hao Huang; Robert W Sprung; W Sean Davidson; Rafael S Czepielewski; Mary Wohltmann; Mary G Sorci-Thomas; Brad W Warner; Gwendalyn J Randolph Journal: Science Date: 2021-07-23 Impact factor: 47.728
Authors: Allie E Steinberger; Maria E Tecos; Hannah M Phelps; Deborah C Rubin; Nicholas O Davidson; Jun Guo; Brad W Warner Journal: Am J Physiol Gastrointest Liver Physiol Date: 2022-06-21 Impact factor: 4.871
Authors: Emily J Onufer; Rafael S Czepielewski; Yong-Hyun Han; Cathleen M Courtney; Stephanie Sutton; Anne Sescleifer; Gwendalyn J Randolph; Brad W Warner Journal: Sci Rep Date: 2022-07-07 Impact factor: 4.996