Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany; German Center for Diabetes Research, München-Neuherberg, 85764 Neuherberg, Germany.
Laboratory of Protein Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Biochem Biophys Res Commun. 2018 Nov 17;506(1):259-265. doi: 10.1016/j.bbrc.2018.10.092. Epub 2018 Oct 19.
Intestinal release of dietary triglycerides via chylomicrons is the major contributor to elevated postprandial triglyceride levels. Dietary lipids can be transiently stored in cytosolic lipid droplets (LDs) located in intestinal enterocytes for later release. ADP ribosylation factor-related protein 1 (ARFRP1) participates in processes of LD growth in adipocytes and in lipidation of lipoproteins in liver and intestine. This study aims to explore the impact of ARFRP1 on LD organization and its interplay with chylomicron-mediated triglyceride release in intestinal-like Caco-2 cells. Suppression of Arfrp1 reduced release of intracellularly derived triglycerides (0.69-fold) and increased the abundance of transitional endoplasmic reticulum ATPase TERA/VCP, fatty acid synthase-associated factor 2 (FAF2) and perilipin 2 (Plin2) at the LD surface. Furthermore, TERA/VCP and FAF2 co-occurred more frequently with ATGL at LDs, suggesting a reduced adipocyte triglyceride lipase (ATGL)-mediated lipolysis. Accordingly, inhibition of lipolysis reduced lipid release from intracellular storage pools by the same magnitude as Arfrp1 depletion. Thus, the lack of Arfrp1 increases the abundance of lipolysis-modulating enzymes TERA/VCP, FAF2 and Plin2 at LDs, which might decrease lipolysis and reduce availability of fatty acids for triglyceride synthesis and their release via chylomicrons.
膳食三酰甘油通过乳糜微粒从肠道释放是餐后甘油三酯水平升高的主要原因。膳食脂质可以暂时储存在位于肠上皮细胞中的细胞质脂滴 (LD) 中，以备后用。ADP 核糖基化因子相关蛋白 1 (ARFRP1) 参与脂肪细胞中 LD 的生长和肝脏及肠道中脂蛋白的脂质化过程。本研究旨在探讨 ARFRP1 对 LD 组织的影响及其与肠样 Caco-2 细胞中乳糜微粒介导的甘油三酯释放的相互作用。Arfrp1 的抑制减少了细胞内源性甘油三酯的释放 (0.69 倍)，并增加了过渡性内质网 ATP 酶 TERA/VCP、脂肪酸合成酶相关因子 2 (FAF2) 和 perilipin 2 (Plin2) 在 LD 表面的丰度。此外，TERA/VCP 和 FAF2 与 LD 上的 ATGL 更频繁地共存，表明脂肪细胞甘油三酯脂肪酶 (ATGL) 介导的脂解作用减少。因此，脂解抑制减少了细胞内储存池的脂质释放，其程度与 Arfrp1 耗竭相同。因此，缺乏 Arfrp1 会增加脂解调节酶 TERA/VCP、FAF2 和 Plin2 在 LD 中的丰度，这可能会降低脂解作用并减少脂肪酸用于甘油三酯合成及其通过乳糜微粒释放的可用性。
