Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
J Lipid Res. 2023 Dec;64(12):100461. doi: 10.1016/j.jlr.2023.100461. Epub 2023 Oct 14.
Perilipin 2 (Plin2) binds to the surface of hepatic lipid droplets (LDs) with expression levels that correlate with triacylglyceride (TAG) content. We investigated if Plin2 is important for hepatic LD storage in fasted or high-fat diet-induced obese Plin2 and Plin2 mice. Plin2 mice had comparable body weights, metabolic phenotype, glucose tolerance, and circulating TAG and total cholesterol levels compared with Plin2 mice, regardless of the dietary regime. Both fasted and high-fat fed Plin2 mice stored reduced levels of hepatic TAG compared with Plin2 mice. Fasted Plin2 mice stored fewer but larger hepatic LDs compared with Plin2 mice. Detailed hepatic lipid analysis showed substantial reductions in accumulated TAG species in fasted Plin2 mice compared with Plin2 mice, whereas cholesteryl esters and phosphatidylcholines were increased. RNA-Seq revealed minor differences in hepatic gene expression between fed Plin2 and Plin2 mice, in contrast to marked differences in gene expression between fasted Plin2 and Plin2 mice. Our findings demonstrate that Plin2 is required to regulate hepatic LD size and storage of neutral lipid species in the fasted state, while its role in obesity-induced steatosis is less clear.
脂滴包被蛋白 2（Plin2）与肝内脂滴（LDs）表面结合，其表达水平与三酰甘油（TAG）含量相关。我们研究了 Plin2 在禁食或高脂饮食诱导肥胖的 Plin2 和 Plin2 小鼠的肝 LD 储存中是否重要。无论饮食方案如何，Plin2 小鼠的体重、代谢表型、葡萄糖耐量、循环 TAG 和总胆固醇水平与 Plin2 小鼠相当。与 Plin2 小鼠相比，禁食和高脂喂养的 Plin2 小鼠储存的肝 TAG 水平降低。与 Plin2 小鼠相比，禁食的 Plin2 小鼠储存的肝 LD 数量较少，但体积较大。详细的肝脂分析显示，与 Plin2 小鼠相比，禁食的 Plin2 小鼠中积累的 TAG 种类显著减少，而胆固醇酯和磷脂酰胆碱增加。RNA-Seq 显示，与禁食的 Plin2 和 Plin2 小鼠之间的基因表达存在显著差异相比，在喂食的 Plin2 和 Plin2 小鼠之间的肝基因表达差异较小。我们的研究结果表明，Plin2 是调节肝 LD 大小和禁食时中性脂质储存所必需的，而其在肥胖诱导的脂肪变性中的作用尚不清楚。
