Sinton, Matthew C. and Meseguer-Ripolles, Jose and Lucendo-Villarin, Baltasar and Wernig-Zorc, Sara and Thomson, John P. and Carter, Roderick N. and Lyall, Marcus J. and Walker, Paul D. and Thakker, Alpesh and Meehan, Richard R. and Lavery, Gareth G. and Morton, Nicholas M. and Ludwig, Christian and Tennant, Daniel A. and Hay, David C. and Drake, Amanda J. (2021) A human pluripotent stem cell model for the analysis of metabolic dysfunction in hepatic steatosis. ISCIENCE, 24 (1): 101931. ISSN , 2589-0042
Full text not available from this repository. (Request a copy)Abstract
Nonalcoholic fatty liver disease (NAFLD) is currently the most prevalent form of liver disease worldwide. This term encompasses a spectrum of pathologies, from benign hepatic steatosis to non-alcoholic steatohepatitis, which have, to date, been challenging to model in the laboratory setting. Here, we present a human pluripotent stem cell (hPSC)-derived model of hepatic steatosis, which overcomes inherent challenges of current models and provides insights into the metabolic rewiring associated with steatosis. Following induction of macrovesicular steatosis in hepatocyte-like cells using lactate, pyruvate, and octanoate (LPO), respirometry and transcriptomic analyses revealed compromised electron transport chain activity. C-13 isotopic tracing studies revealed enhanced TCA cycle anaplerosis, with concomitant development of a compensatory purine nucleotide cycle shunt leading to excess generation of fumarate. This model of hepatic steatosis is reproducible, scalable, and overcomes the challenges of studying mitochondrial metabolism in currently available models.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NONALCOHOLIC FATTY LIVER; ACTIVATED PROTEIN-KINASE; OXIDATIVE STRESS; LIPID-METABOLISM; TCA CYCLE; MITOCHONDRIAL DYSFUNCTION; INSULIN-RESISTANCE; DISEASE; 5-HYDROXYMETHYLCYTOSINE; EXPRESSION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Sep 2022 06:30 |
| Last Modified: | 23 Sep 2022 06:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47910 |
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