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Altered hepatic lipid droplet morphology and lipid metabolism in fasted Plin2 null mice.
Journal of Lipid Research ( IF 6.5 ) Pub Date : 2023-10-14 , DOI: 10.1016/j.jlr.2023.100461
Atanaska I Doncheva 1 , Yuchuan Li 2 , Prabhat Khanal 3 , Marit Hjorth 1 , Svein O Kolset 1 , Frode A Norheim 1 , Alan R Kimmel 4 , Knut Tomas Dalen 5
Affiliation  

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 to Plin2+/+ mice, regardless of the dietary regime. Both fasted and high-fat fed Plin2-/- mice stored reduced levels of hepatic TAG compared to Plin2+/+ mice. Fasted Plin2-/- mice stored fewer, but larger hepatic lipid droplets compared to Plin2+/+ mice. Detailed hepatic lipid analysis showed substantial reductions in accumulated TAG species in fasted Plin2-/- mice compared to Plin2+/+ mice, whereas cholesteryl esters and phosphatidylcholines were increased. RNA sequencing 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 lipid droplet size and storage of neutral lipid species in the fasted state, while its role in obesity-induced steatosis is less clear.

中文翻译:

禁食 Plin2 缺失小鼠的肝脏脂滴形态和脂质代谢发生改变。

Perilipin 2 (Plin2) 与肝脂滴 (LD) 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 对于禁食或高脂饮食诱导的肥胖 Plin2 +/+和 Plin2 -/-小鼠的肝脏 LD 储存是否重要。无论饮食方案如何,与 Plin2 +/+小鼠相比, Plin2 -/-小鼠的体重、代谢表型、葡萄糖耐量以及循环 TAG 和总胆固醇水平相当。与 Plin2 +/+小鼠相比,禁食和高脂喂养的 Plin2 -/-小鼠肝脏 TAG 水平均降低。与 Plin2 +/+小鼠相比,禁食的 Plin2 -/-小鼠肝脏储存的脂滴较少,但较大。详细的肝脂质分析显示,与 Plin2 +/+小鼠相比,禁食的 Plin2 -/-小鼠中积累的 TAG 种类大幅减少,而胆固醇酯和磷脂酰胆碱则增加。RNA测序显示,进食的Plin2 +/+和Plin2 -/-小鼠之间的肝脏基因表达存在微小差异,而禁食的Plin2 +/+和Plin2 -/-小鼠之间的基因表达存在显着差异。我们的研究结果表明,在禁食状态下,Plin2 是调节肝脏脂滴大小和中性脂质种类储存所必需的,但其在肥胖引起的脂肪变性中的作用尚不清楚。
更新日期:2023-10-14
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