Overweight has become a major health care problem in Western societies and is
accompanied by an increasing incidence and prevalence of non-alcoholic fatty liver disease (NAFLD).
The progression from NAFLD to non-alcoholic steatohepatitis (NASH) marks a crucial tipping point
in the progression of severe and irreversible liver diseases. This study aims to gain further insight
into the molecular processes leading to the evolution from steatosis to steatohepatitis. Steatosis was
induced in cultures of primary human hepatocytes by continuous five-day exposure to free fatty
acids (FFAs). The kinetics of lipid accumulation, lipotoxicity, and oxidative stress were measured.
Additionally, ER stress was evaluated by analyzing the protein expression profiles of its key players:
PERK, IRE1a, and ATF6a. Our data revealed that hepatocytes are capable of storing enormous
amounts of lipids without showing signs of lipotoxicity. Prolonged lipid accumulation did not create
an imbalance in hepatocyte redox homeostasis or a reduction in antioxidative capacity. However, we
observed an FFA-dependent increase in ER stress, revealing thresholds for triggering the activation of
pathways associated with lipid stress, inhibition of protein translation, and apoptosis. Our study
clearly showed that even severe lipid accumulation can be attenuated by cellular defenses, but
regenerative capacities may be reduced.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:90126 |
| Date | 26 February 2024 |
| Creators | Rennert, Christiane, Heil, Theresa, Schicht, Gerda, Stilkerich, Anna, Seidemann, Lena, Kegel-Hübner, Victoria, Seehofer, Daniel, Damm, Georg |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 7097, 10.3390/ijms21197097 |
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