Sugar Crush

Metabolism-Induced Sinusoidal Endothelial Cell Defenestration as Critical Determinant of Fatty Liver Disease Progression

The Sugar Crush project aims to investigate the role of the endothelial cell of the liver in progression of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the major clinical challenges of the 21st century. For decades research focused on hepatocytes, but failed to unravel the mechanisms behind disease progression, while largely overlooking the role of the endothelial cell of the liver, the LSEC. LSECs, which form the walls of the hepatic sinusoids, contain small pores, or fenestrations, which facilitate the transfer of substrates between blood and hepatocytes. A ubiquitous clinical observation in the progression of NAFLD is the loss of fenestrations, which importantly precedes the onset of fibrosis, collagen "scar" tissue that is eliminated primarily by LSECs. The mechanisms responsible for LSEC defenestration in NAFLD progression have yet to be described. 

We aim to investigate the metabolism-based molecular mechanisms underlying changes in LSEC morphology and function during initiation and progression of NAFLD, using animal models and human clinical samples. 

The main challenge is the need to independently manipulate and probe metabolic pathway utilization and morphological and functional changes in these cells. To overcome this challenge, the project will combine multidisciplinary approaches in cellular biology, genetics, and physics, and the expertise of a research team composed of top-of-the-field local, national and international collaborators. 

The project is anticipated to make a tremendous scientific impact, and have the potential for clinical ramifications


Cristina Ionica Øie (Principal investigator)
Gianina Dumitriu
Gahl Levy

Financial/grant information:

Funding: Norwegian Research Council (NRC)