Cianflone Katherine, Paglialunga Sabina, Roy Christian
Department of Biochemistry, McGill University, Montreal, Canada.
Atheroscler Suppl. 2008 Sep;9(2):63-8. doi: 10.1016/j.atherosclerosissup.2008.05.014. Epub 2008 Aug 6.
Various dietary factors affect postprandial metabolism yet precise mechanisms have not necessarily been pinpointed. The effects of various meal components on postprandial lipemia lead to the following question: do we need a standardized oral lipid tolerance test? A number of transporters, enzymes, receptors and hormones directly influence and act as "gatekeepers" of these processes. Each protein appears to have specific and individual functional roles in the overall process and selected developments in these areas will be reviewed. Within the intestinal cells, FABP2 (fatty acid-binding protein 2) and MTP (microsomal triglyceride transfer protein) are required for the formation of chylomicrons. Niemann-Pick C1-like 1 (NPC1-L1) plays an important role in cholesterol absorption and provides a pharmacological target. Hormones such as GLP1 and GLP2 influence this absorption process. Within the periphery, lipoprotein lipase (LPL) is a key gatekeeper of clearance. Of the massive amounts of fatty acids released by LPL, 36% escape peripheral adipose and muscle uptake and fatty acid overload can result in LPL product inhibition. Acylation stimulating protein (ASP) and insulin are two key hormones in maintaining efficient tissue uptake and re-esterification of fatty acids while TNFalpha negatively influences this process. In both ASP deficient (C3 KO) and C5L2 KO mice, postprandial lipemia increased with reduced adipose tissue storage. This is compensated by increased energy expenditure and muscle lipid oxidation. Clearance of hepatic remnants is controlled through many factors, including SR-B1 and ABCA1. Intestinal, peripheral and hepatic gatekeepers serve important and individual roles in regulating postprandial lipemia and provide potential targets for regulation.
多种饮食因素会影响餐后代谢，但确切机制尚未完全明确。各种膳食成分对餐后血脂的影响引发了以下问题：我们是否需要标准化的口服脂质耐量试验？许多转运蛋白、酶、受体和激素直接影响这些过程并充当“守门人”。每种蛋白质在整个过程中似乎都具有特定的功能作用，本文将综述这些领域的一些最新进展。在肠细胞内，乳糜微粒的形成需要脂肪酸结合蛋白2（FABP2）和微粒体甘油三酯转运蛋白（MTP）。尼曼-皮克C1样1蛋白（NPC1-L1）在胆固醇吸收中起重要作用，并提供了一个药理学靶点。胰高血糖素样肽1（GLP1）和胰高血糖素样肽2（GLP2）等激素会影响这一吸收过程。在周围组织中，脂蛋白脂肪酶（LPL）是清除过程的关键守门人。LPL释放的大量脂肪酸中，36%无法被周围脂肪和肌肉摄取，脂肪酸过载会导致LPL产物抑制。酰化刺激蛋白（ASP）和胰岛素是维持脂肪酸有效组织摄取和再酯化的两种关键激素，而肿瘤坏死因子α（TNFα）则对这一过程产生负面影响。在ASP缺陷（C3基因敲除）和C5L2基因敲除小鼠中，餐后血脂升高，脂肪组织储存减少。这通过增加能量消耗和肌肉脂质氧化得到补偿。肝内残余物的清除受多种因素控制，包括清道夫受体B1（SR-B1）和ATP结合盒转运体A1（ABCA1）。肠道、外周和肝脏的守门人在调节餐后血脂方面发挥着重要且各自独特的作用，并提供了潜在的调节靶点。
