Activities per year
Methods: PHH, hSKP-HPC and HepaRG cultures were exposed to NASH-inducing triggers (insulin, glucose, sodium oleate, palmitic acid, TNF-α, IL-1β and TGF-β) with or without elafibranor for 24h. Hereafter, whole-genome microarrays (Affymetrix) were performed and used for pathway analysis. Publicly-available transcriptomic data of clinical samples of NASH patients and patients with resolved NASH after bariatric surgery served as benchmarks.
Results: Hepatic ‘NASH-induced’ cultures showed up to 35% overlap with transcriptional signatures present in samples of NASH patients, indicating the relevance of the in vitro models. In all in vitro models, elafibranor restricted NASH-specific cellular processes through the activation and inhibition of processes also seen in pre- and post- bariatric surgery samples of NASH patients. PPARGC1A, PPARA and SIRT1 were identified as common upstream regulators in the three in vitro models exposed to elafibranor. Elafibranor induced upregulation of PLIN2, PDK4 and ANGPTL4, which have been earlier linked to liver steatosis, under regulation of the common upstream regulators. These pro-steatogenic mediators were, however, not increased in liver samples of patients with resolved NASH.
Conclusions: Modulations of ANGPTL4, PDK4 and PLIN2 deserve further attention in the preclinical investigation of PPAR-agonists for the treatment of NASH.
|Title of host publication||3rd European Fatty Liver Conference (EFLC2022)|
|Subtitle of host publication||Interorgan connection in NAFLD – from basic science to a multidisciplinary clinical approach|
|Publisher||3rd European Fatty Liver Conference|
|Number of pages||1|
|Publication status||Published - 10 Jun 2022|
|Event||3rd European Fatty Liver Conference - Maastricht, Netherlands|
Duration: 8 Jun 2022 → 10 Jun 2022
|Conference||3rd European Fatty Liver Conference|
|Period||8/06/22 → 10/06/22|
- Preclinical research
FingerprintDive into the research topics of 'Human hepatic in vitro models identify ANGPTL4, PDK4 and PLIN2 as potential pro-steatogenic mediators induced by elafibranor'. Together they form a unique fingerprint.
- 1 Talk or presentation at a conference
Human hepatic in vitro models identify ANGPTL4, PDK4 and PLIN2 as potential pro-steatogenic mediators induced by elafibranor
Joost Boeckmans (Speaker), Alexandra Gatzios (Contributor), Anja Heymans (Contributor), Matthias Rombaut (Contributor), Vera Rogiers (Contributor), Joery De Kock (Contributor), Tamara Vanhaecke (Contributor) & Robim Marcelino Rodrigues (Contributor)9 Jun 2022
Activity: Talk or presentation › Talk or presentation at a conferenceFile