Differential Lipotoxic Effects of Palmitate and Oleate in Activated Human Hepatic Stellate Cells and Epithelial Hepatoma Cells
| Autor: | Nica M. Borradaile, Cynthia G. Sawyez, Alexandra M. Hetherington, Emma Zilberman, Debra L. Robson, Alexandra M. Stoianov |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cirrhosis Physiology Hepatoma cells Primary Cell Culture Palmitic Acid Gastroenterology lcsh:Physiology Transcriptome lcsh:Biochemistry 03 medical and health sciences Stress Physiological Fibrosis Internal medicine NAFLD Nonalcoholic fatty liver disease Hepatic Stellate Cells medicine Humans lcsh:QD415-436 RNA Messenger Fatty acids Oligonucleotide Array Sequence Analysis Activated hepatic stellate cells Cell Death lcsh:QP1-981 Chemistry Cell Polarity Hep G2 Cells Endoplasmic Reticulum Stress Lipid Metabolism medicine.disease 3. Good health Cytoskeletal Proteins 030104 developmental biology Gene Expression Regulation Lipotoxicity Organ Specificity Cell culture Hepatocellular carcinoma Cancer research Hepatic stellate cell Carrier Proteins Oxidation-Reduction Oleic Acid |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 39, Iss 4, Pp 1648-1662 (2016) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypothesized that primary human activated hepatic stellate cells and epithelial hepatoma (HepG2) cells respond differently to lipotoxic conditions, and investigated the mechanisms involved. Methods: Primary activated hepatic stellate cells and HepG2 cells were exposed to pathophysiological concentrations of fatty acids and comparative studies of lipid metabolic and stress response pathways were performed. Results: Both cell types remained proliferative during exposure to a combination of palmitate plus oleate reflective of the general saturated versus unsaturated fatty acid composition of western diets. However, exposure to either high palmitate or high oleate alone induced cytotoxicity in activated stellate cells, while only palmitate caused cytotoxicity in HepG2 cells. mRNA microarray and biochemical comparisons revealed that stellate cells stored markedly less fatty acids as neutral lipids, and had reduced capacity for beta-oxidation. Similar to previous observations in HepG2 cells, palmitate, but not oleate, induced ER stress and actin stress fiber formation in activated stellate cells. In contrast, oleate, but not palmitate, induced the inflammatory signal TXNIP, decreased cytoskeleton proteins, and decreased cell polarity preceding cell death in activated stellate cells. Conclusions: Palmitate-induced lipotoxicity was associated with ER stress pathways in both primary activated hepatic stellate cells and epithelial hepatoma cells, whereas high oleate caused lipotoxicity only in activated stellate cells, possibly through a distinct mechanism involving disruption of cytoskeleton components. This may have implications for optimal dietary fatty acid compositions during various stages of NAFLD. |
| Databáze: | OpenAIRE |
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