Darimont C, Gradoux N, de Pover A
Metabolic and Cardiovascular Diseases, Novartis Pharma AG, CH-4002 Basel, Switzerland.
Am J Physiol. 1999 Mar;276(3):G606-12. doi: 10.1152/ajpgi.1999.276.3.G606.
Epidermal growth factor (EGF) has been reported to stimulate carbohydrate, amino acid, and electrolyte transport in the small intestine, but its effects on lipid transport are poorly documented. This study aimed to investigate EGF effects on fatty acid uptake and esterification in a human enterocyte cell line (Caco-2). EGF inhibited cell uptake of [14C]palmitate and markedly reduced its incorporation into triglycerides. In contrast, the incorporation in phospholipids was enhanced. To elucidate the mechanisms involved, key steps of lipid synthesis were investigated. The amount of intestinal fatty acid-binding protein (I-FABP), which is thought to be important for fatty acid absorption, and the activity of diacylglycerol acyltransferase (DGAT), an enzyme at the branch point of diacylglycerol utilization, were reduced. EGF effects on DGAT and on palmitate esterification occurred at 2-10 ng/ml, whereas effects on I-FABP and palmitate uptake occurred only at 10 ng/ml. This suggests that EGF inhibited palmitate uptake by reducing the I-FABP level and shifted its utilization from triglycerides to phospholipids by inhibiting DGAT. This increase in phospholipid synthesis might play a role in the restoration of enterocyte absorption function after intestinal mucosa injury.
表皮生长因子(EGF)已被报道可刺激小肠中的碳水化合物、氨基酸和电解质转运,但其对脂质转运的影响却鲜有文献记载。本研究旨在探讨EGF对人肠上皮细胞系(Caco-2)中脂肪酸摄取和酯化的影响。EGF抑制了[14C]棕榈酸的细胞摄取,并显著降低了其掺入甘油三酯的量。相反,其掺入磷脂的量增加。为阐明其中涉及的机制,对脂质合成的关键步骤进行了研究。肠道脂肪酸结合蛋白(I-FABP)的量被认为对脂肪酸吸收很重要,而二酰甘油酰基转移酶(DGAT)是二酰甘油利用分支点处的一种酶,其活性降低。EGF对DGAT和棕榈酸酯化的影响在2-10 ng/ml时出现,而对I-FABP和棕榈酸摄取的影响仅在10 ng/ml时出现。这表明EGF通过降低I-FABP水平抑制了棕榈酸摄取,并通过抑制DGAT将其利用从甘油三酯转向磷脂。磷脂合成的这种增加可能在肠黏膜损伤后肠上皮细胞吸收功能的恢复中起作用。