Department of Nutritional Sciences, Rutgers, the State University of New Jersey, New Brunswick, USA.
Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G803-14. doi: 10.1152/ajpgi.00229.2010. Epub 2011 Feb 24.
It has long been known that mammalian enterocytes coexpress two members of the fatty acid-binding protein (FABP) family, the intestinal FABP (IFABP) and the liver FABP (LFABP). Both bind long-chain fatty acids and have similar though not identical distributions in the intestinal tract. While a number of in vitro properties suggest the potential for different functions, the underlying reasons for expression of both proteins in the same cells are not known. Utilizing mice genetically lacking either IFABP or LFABP, we directly demonstrate that each of the enterocyte FABPs participates in specific pathways of intestinal lipid metabolism. In particular, LFABP appears to target fatty acids toward oxidative pathways and dietary monoacylglycerols toward anabolic pathways, while IFABP targets dietary fatty acids toward triacylglycerol synthesis. The two FABP-null models also displayed differences in whole body response to fasting, with LFABP-null animals losing less fat-free mass and IFABP-null animals losing more fat mass relative to wild-type mice. The metabolic changes observed in both null models appear to occur by nontranscriptional mechanisms, supporting the hypothesis that the enterocyte FABPs are specifically trafficking their ligands to their respective metabolic fates.
长期以来，人们一直知道哺乳动物肠细胞同时表达脂肪酸结合蛋白 (FABP) 家族的两个成员，即肠型脂肪酸结合蛋白 (IFABP) 和肝型脂肪酸结合蛋白 (LFABP)。这两种蛋白都能结合长链脂肪酸，在肠道中的分布也相似但不完全相同。尽管许多体外特性表明它们可能具有不同的功能，但在同一细胞中表达这两种蛋白的潜在原因尚不清楚。利用基因敲除 IFABP 或 LFABP 的小鼠，我们直接证明了肠细胞 FABP 中的每一种都参与了特定的肠道脂质代谢途径。特别是 LFABP 似乎将脂肪酸靶向氧化途径，将膳食单酰甘油靶向合成代谢途径，而 IFABP 将膳食脂肪酸靶向三酰甘油合成。这两种 FABP 敲除模型在对禁食的全身反应方面也表现出差异，LFABP 敲除动物相对于野生型小鼠丢失的无脂体重较少，IFABP 敲除动物丢失的脂肪体重较多。在这两种敲除模型中观察到的代谢变化似乎是通过非转录机制发生的，这支持了肠细胞 FABP 专门将其配体转运到各自代谢命运的假说。
