A1 Refereed original research article in a scientific journal
Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein
Authors: Hansen, Daniel; Jensen, Jasmin E.R.; Andersen, Christian A.T.; Jakobsgaard, Peter R.; Havelund, Jesper; Lauritsen, Line; Mandacaru, Samuel; Siersbaek, Majken; Shackleton, Oliver L.; Inoue, Hiroshi; Brewer, Jonathan R.; Schwabe, Robert F.; Blagoev, Blagoy; Færgeman, Nils J.; Salmi, Marko; Ravnskjaer, Kim
Publisher: Cell Press
Publishing place: CAMBRIDGE
Publication year: 2025
Journal: Cell Metabolism
Journal name in source: Cell Metabolism
Journal acronym: CELL METAB
Volume: 37
Issue: 4
First page : 971
Last page: 986
Number of pages: 25
ISSN: 1550-4131
eISSN: 1932-7420
DOI: https://doi.org/10.1016/j.cmet.2025.01.022
Web address : https://doi.org/10.1016/j.cmet.2025.01.022
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/491571840
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.
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