南丹麦大学Kim Ravnskjaer小组宣布他们的最新研究探明了肝星状细胞通过质膜囊泡相关蛋白调节肝脏脂肪酸利用。相关论文于2025年3月3日发表在《细胞—代谢》杂志上。

研究组发现小鼠肝星状细胞（HSC）及其丰富表达的质膜囊泡相关蛋白（PLVAP）控制着肝脏底物对空腹能量代谢的偏好。HSC特异性消融小鼠PLVAP可升高肝脏胰岛素信号并改善葡萄糖耐量。禁食的HSC PLVAP敲除小鼠显示肝脏脂肪酸酯化成二甘油酯和三甘油酯受到抑制，将空腹代谢从脂肪酸氧化转变为对碳水化合物的依赖。通过超分辨率显微镜，该课题组人员将HSC PLVAP定位到位于窦窦管腔的小窝中，支持HSC和PLVAP膜小窝在肝脏正常空腹代谢中的作用。

据介绍，在禁食期间，肝脏对正常的脂肪酸利用是必不可少的。循环脂肪酸被肝细胞吸收并酯化为三酰基甘油，用于氧化代谢和生酮或输出。虽然脂肪酸氧化在肝细胞中的调控已被很好地理解，但肝细胞对非酯化脂肪酸的摄取和保留尚不清楚。

附：英文原文

Title: Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein

Author: Daniel Hansen, Jasmin E.R. Jensen, Christian A.T. Andersen, Peter R. Jakobsgaard, Jesper Havelund, Line Lauritsen, Samuel Mandacaru, Majken Siersbaek, Oliver L. Shackleton, Hiroshi Inoue, Jonathan R. Brewer, Robert F. Schwabe, Blagoy Blagoev, Nils J. Frgeman, Marko Salmi, Kim Ravnskjaer

Issue&Volume: 2025-03-03

Abstract: The liver is essential for normal fatty acid utilization during fasting. Circulating fatty acids are taken up by hepatocytes and esterified as triacylglycerols for either oxidative metabolization and ketogenesis or export. Whereas the regulation of fatty acid oxidation in hepatocytes is well understood, the uptake and retention of non-esterified fatty acids by hepatocytes is not. Here, we show that murine hepatic stellate cells (HSCs) and their abundantly expressed plasmalemma vesicle-associated protein (PLVAP) control hepatic substrate preference for fasting energy metabolism. HSC-specific ablation of PLVAP in mice elevated hepatic insulin signaling and improved glucose tolerance. Fasted HSC PLVAP knockout mice showed suppressed hepatic fatty acid esterification into di- and triacylglycerols, shifting fasting metabolism from fatty acid oxidation to reliance on carbohydrates. By super-resolution microscopy, we localized HSC PLVAP to caveolae residing along the sinusoidal lumen, supporting a role for HSCs and PLVAP-diaphragmed caveolae in normal fasting metabolism of the liver.

DOI: 10.1016/j.cmet.2025.01.022

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00022-1