Drozdowski Laurie A, Dixon Walter T, McBurney Michael I, Thomson Alan B R
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada.
JPEN J Parenter Enteral Nutr. 2002 May-Jun;26(3):145-50. doi: 10.1177/0148607102026003145.
The supplementation of total parenteral nutrition (TPN) formulas with short-chain fatty acids (SCFAs) increases glucose uptake and the expression of glucose transporters in parenterally fed animals. Several signals may be involved in intestinal adaptation; however, increased messenger RNA (mRNA) levels for proglucagon and several early-response genes, including c-myc and c-fos, are seen in animals receiving SCFA-supplemented TPN. Although the effects of a mixture of SCFAs are well documented, the relative contribution of individual SCFAs is unknown. Butyrate is a preferred fuel of colonocytes, with documented effects on cellular proliferation and gene expression. Accordingly, this study was undertaken to determine the relative role of butyrate in initiating an adaptive response in nonresected rats receiving TPN.
Animals received standard TPN for 66 hours, followed by 6 hours of either standard TPN, TPN supplemented with a mixture of SCFAs (acetate, propionate, and butyrate, 60 mmol/L total), or TPN supplemented with butyrate alone (9 mmol/L). An oral control group was fed an elemental diet, similar in macronutrient content to the TPN, so that all animals received the same amount of energy daily.
SCFAs increased ileal glucose transporter 2 (GLUT2) mRNA expression compared with the orally fed group. SCFAs also increased proglucagon mRNA expression compared with the TPN group. No changes in Na+K(+)-adenosine triphosphatase or early-response gene expression were found in this study.
In a rat model of TPN, the use of 9 mmol/L butyrate did not have the same effect on GLUT2 and proglucagon expression as a 60-mmol/L mixture of SCFAs. This suggests that the effect of a mixture of SCFAs on intestinal gene expression is not butyrate specific.
在全肠外营养（TPN）配方中添加短链脂肪酸（SCFA）可增加肠外营养动物的葡萄糖摄取及葡萄糖转运蛋白的表达。肠道适应可能涉及多种信号；然而，在接受补充SCFA的TPN的动物中，胰高血糖素原及包括c-myc和c-fos在内的几种早期反应基因的信使核糖核酸（mRNA）水平升高。尽管SCFA混合物的作用已有充分记录，但单个SCFA的相对贡献尚不清楚。丁酸盐是结肠细胞的首选燃料，对细胞增殖和基因表达有明确影响。因此，本研究旨在确定丁酸盐在接受TPN的未切除大鼠中引发适应性反应的相对作用。
动物接受标准TPN 66小时，随后6小时给予标准TPN、补充SCFA混合物（乙酸盐、丙酸盐和丁酸盐，总量60 mmol/L）的TPN或仅补充丁酸盐（9 mmol/L）的TPN。口服对照组给予要素饮食，其宏量营养素含量与TPN相似，以便所有动物每日摄入相同量的能量。
与口服喂养组相比，SCFA增加了回肠葡萄糖转运蛋白2（GLUT2）mRNA表达。与TPN组相比，SCFA也增加了胰高血糖素原mRNA表达。本研究未发现钠钾ATP酶或早期反应基因表达有变化。
在TPN大鼠模型中，使用9 mmol/L丁酸盐对GLUT2和胰高血糖素原表达的影响与60 mmol/L SCFA混合物不同。这表明SCFA混合物对肠道基因表达的影响并非丁酸盐特异性的。
