Onufer Emily J, Han Yong-Hyun, Czepielewski Rafael S, Courtney Cathleen M, Sutton Stephanie, Randolph Gwendalyn J, Warner Brad W
Division of Pediatric Surgery, Department of Surgery, St. Louis Children's Hospital, Washington University in St. Louis School of Medicine, St. Louis, MO.
Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO.
J Pediatr Surg. 2020 Jun;55(6):1099-1106. doi: 10.1016/j.jpedsurg.2020.02.037. Epub 2020 Feb 28.
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.
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.
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.
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.
短肠综合征(SBS)患儿肠内营养支持的最佳方案尚未明确。理论上,高脂肪肠内饮食因热量密度增加和结构适应性增强而有益。因此,我们试图确定与标准饲料(SC)饮食相比,高脂肪饮食(HFD)对SBS常见并发症肝损伤的长期影响。
使用与肠外营养无关的切除相关肝损伤模型,C57BL/6小鼠接受假手术或50%或75%近端小肠切除术(SBR)。然后,每组小鼠分别喂食HFD(35%千卡脂肪)或SC(13%千卡脂肪)。在术后第15周,对肝损伤标志物进行定量分析。
与假手术、50%和75%切除组中喂食SC的小鼠相比,喂食HFD的小鼠肝脏甘油三酯水平增加了7至19倍。仅在喂食HFD的切除小鼠中,血清ALT(75%切除小鼠比假手术对照组增加2.2倍)和AST(50%和75%切除小鼠分别增加2.0倍和2.7倍)水平以及肝纤维化染色升高。
在我们的小鼠SBS模型中,长期肠内喂食HFD与肝脂肪变性和肝损伤有关。我们观察到肝脂肪变性和损伤的发生与肠外营养无关,这表明肠内喂养成分和肠道损失程度可能对肠衰竭相关肝病有重大影响。