We previously reported that overexpression of full-length cholesteryl ester transfer protein (FL-CETP), but not its exon 9-deleted variant (∆E9-CETP), in an adipose cell line reduces their triacylglycerol (TAG) content. This provided mechanistic insight into several in vivo studies where FL-CETP levels are inversely correlated with adiposity. However, increased FL-CETP is also associated with elevated hepatic lipids, suggesting that the effect of CETP on cellular lipid metabolism may be tissue-specific. Here, we directly investigated the role of FL-CETP and ∆E9-CETP in hepatic lipid metabolism. FL- or ∆E9-CETP was overexpressed in HepG2-C3A by adenovirus transduction. Overexpression of either FL or ∆E9-CETP in hepatocytes increased cellular TAG mass by 25% but reduced TAG secretion. This cellular TAG was contained in larger and more numerous lipid droplets. Analysis of TAG synthetic and catabolic pathways showed that this elevated TAG content was due to increased incorporation of fatty acid into TAG (24%), and higher de novo synthesis of fatty acid (50%) and TAG from acetate (40%). siRNA knockdown of CETP had the opposite effect on TAG synthesis and lipogenesis, and decreased cellular TAG. This novel increase in cellular TAG by FL-CETP overexpression was reproduced in Caco-2 intestinal epithelial cells. We conclude that, unlike that seen in adipocyte cells, overexpression of either CETP isoform in lipoprotein-secreting cells promotes the accumulation of TAG. These data suggest that the in vivo correlation between CETP levels and hepatic steatosis can be explained, in part, by a direct effect of CETP on hepatocyte cellular metabolism.

中文翻译：

---

全长胆固醇酯转移蛋白和外显子 9 缺失的胆固醇酯转移蛋白均促进培养的肝细胞中甘油三酯的储存

我们之前报道过，在脂肪细胞系中过表达全长胆固醇酯转移蛋白 (FL-CETP) 而不是其外显子 9 缺失变体 (ΔE9-CETP) 会降低其三酰甘油 (TAG) 含量。这提供了对 FL-CETP 水平与肥胖呈负相关的几项体内研究的机制洞察。然而，增加的 FL-CETP 也与升高的肝脏脂质有关，表明 CETP 对细胞脂质代谢的影响可能是组织特异性的。在这里，我们直接研究了 FL-CETP 和 ΔE9-CETP 在肝脏脂质代谢中的作用。FL-或 ΔE9-CETP 通过腺病毒转导在 HepG2-C3A 中过表达。肝细胞中 FL 或 ΔE9-CETP 的过表达使细胞 TAG 质量增加了 25%，但减少了 TAG 分泌。这种细胞标签包含在更大和更多的脂滴中。对 TAG 合成和分解代谢途径的分析表明，这种升高的 TAG 含量是由于脂肪酸掺入 TAG 的增加 (24%)，以及脂肪酸 (50%) 和来自乙酸 (40%) 的 TAG 的更高从头合成。CETP 的 siRNA 敲低对 TAG 合成和脂肪生成有相反的影响，并减少细胞 TAG。这种由 FL-CETP 过表达引起的细胞标记的新增加在 Caco-2 肠上皮细胞中再现。我们得出结论，与在脂肪细胞中看到的不同，CETP 同种型在脂蛋白分泌细胞中的过表达促进了 TAG 的积累。这些数据表明，CETP 水平与肝脂肪变性之间的体内相关性可以部分解释为