Intestinal epithelial cells convert excess fatty acids into triglyceride (TAG) for storage in cytoplasmic lipid droplets and secretion in chylomicrons. Nuclear lipid droplets (nLDs) are present in intestinal cells but their origin and relationship to cytoplasmic TAG synthesis and secretion is unknown. nLDs and related lipid-associated promyelocytic leukemia structures (LAPS) were abundant in oleate-treated Caco2 but less frequent in other human colorectal cancer cell lines and mouse intestinal organoids. nLDs and LAPS in undifferentiated oleate-treated Caco2 cells harbored the phosphatidate phosphatase Lipin1, its product diacylglycerol, and CTP:phosphocholine cytidylyltransferase (CCT)α. CCTα knockout Caco2 cells had fewer but larger nLDs, indicating a reliance on de novo PC synthesis for assembly. Differentiation of Caco2 cells caused large nLDs and LAPS to form regardless of oleate treatment or CCTα expression. nLDs and LAPS in Caco2 cells did not associate with apoCIII and apoAI and formed dependently of microsomal triglyceride transfer protein expression and activity, indicating they are not derived from endoplasmic reticulum luminal LDs precursors. Instead, undifferentiated Caco2 cells harbored a constitutive pool of nLDs and LAPS in proximity to the nuclear envelope that expanded in size and number with oleate treatment. Inhibition of TAG synthesis did affect the number of nascent nLDs and LAPS but prevented their association with promyelocytic leukemia, Lipin1α, and diacylglycerol, which instead accumulated on the nuclear membranes. Thus, nLD and LAPS biogenesis in Caco2 cells is not linked to lipoprotein secretion but involves biogenesis and/or expansion of nascent nLDs by de novo lipid synthesis.

中文翻译：

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CACO2 细胞中的核脂滴源自新生前体并位于核膜原位

肠上皮细胞将多余的脂肪酸转化为甘油三酯（TAG），储存在细胞质脂滴中并分泌在乳糜微粒中。核脂滴 (nLD) 存在于肠细胞中，但其起源以及与细胞质 TAG 合成和分泌的关系尚不清楚。 nLD 和相关的脂质相关早幼粒细胞白血病结构 (LAPS) 在油酸处理的 Caco2 中丰富，但在其他人类结直肠癌细胞系和小鼠肠道类器官中较少出现。未分化油酸处理的 Caco2 细胞中的 nLD 和 LAPS 含有磷脂酸磷酸酶 Lipin1、其产物二酰甘油和 CTP：磷酸胆碱胞苷酰转移酶 (CCT)α。 CCTα 敲除的 Caco2 细胞具有较少但较大的 nLD，表明组装依赖于从头 PC 合成。无论油酸处理或 CCTα 表达如何，Caco2 细胞的分化都会导致大的 nLD 和 LAPS 形成。 Caco2 细胞中的 nLD 和 LAPS 不与 apoCIII 和 apoAI 相关，并且依赖于微粒体甘油三酯转移蛋白的表达和活性而形成，表明它们不是源自内质网管腔 LD 前体。相反，未分化的 Caco2 细胞在核膜附近含有一个由 nLD 和 LAPS 组成的池，通过油酸处理，核膜的大小和数量都会扩大。抑制 TAG 合成确实影响了新生 nLD 和 LAPS 的数量，但阻止了它们与早幼粒细胞白血病、Lipin1α 和二酰甘油的关联，而这些物质反而积聚在核膜上。因此，Caco2细胞中的nLD和LAPS生物发生与脂蛋白分泌无关，但涉及通过从头脂质合成来生物发生和/或新生nLD的扩增。