LSEC Fenestrae Are Preserved Despite Pro-inflammatory Phenotype of Liver Sinusoidal Endothelial Cells in Mice on High Fat Diet

Frontiers in Physiology
Edyta KusStefan Chlopicki

Abstract

Healthy liver sinusoidal endothelial cells (LSECs) maintain liver homeostasis, while LSEC dysfunction was suggested to coincide with defenestration. Here, we have revisited the relationship between LSEC pro-inflammatory response, defenestration, and impairment of LSEC bioenergetics in non-alcoholic fatty liver disease (NAFLD) in mice. We characterized inflammatory response, morphology as well as bioenergetics of LSECs in early and late phases of high fat diet (HFD)-induced NAFLD. LSEC phenotype was evaluated at early (2-8 week) and late (15-20 week) stages of NAFLD progression induced by HFD in male C57Bl/6 mice. NAFLD progression was monitored by insulin resistance, liver steatosis and obesity. LSEC phenotype was determined in isolated, primary LSECs by immunocytochemistry, mRNA gene expression (qRT-PCR), secreted prostanoids (LC/MS/MS) and bioenergetics (Seahorse FX Analyzer). LSEC morphology was examined using SEM and AFM techniques. Early phase of NAFLD, characterized by significant liver steatosis and prominent insulin resistance, was related with LSEC pro-inflammatory phenotype as evidenced by elevated ICAM-1, E-selectin and PECAM-1 expression. Transiently impaired mitochondrial phosphorylation in LSECs was compensated by...Continue Reading

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Citations

May 7, 2020·American Journal of Physiology. Cell Physiology·Xinghui Sun, Edward N Harris
Aug 28, 2020·Frontiers in Physiology·Ekta PandeyEdward N Harris
Sep 29, 2020·Frontiers in Physiology·Alex L WilkinsonShishir Shetty
May 20, 2020·Biophysics Reviews·Bartlomiej ZapotocznyMarek Szymonski
Apr 4, 2021·Journal of Gastroenterology and Hepatology·Yang Wang, Yulan Liu
Apr 15, 2021·Acta Pharmacologica Sinica·Susan Wai Sum Leung, Yi Shi
Mar 15, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Ewelina MatuszykMalgorzata Baranska
Aug 5, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Hui Li

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Methods Mentioned

BETA
AFM
PCR
ELISA

Software Mentioned

Columbus
Fiji
Fiji ImageJ
Columbus Image Data Storage and Analysis System
CellSense
Cell Counter
JPK

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