Stankova 2023 MiP2023

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Stankova 2023 MiP2023

Stankova Pavla
Effect of telmisartan on nutritionally induced nonalcoholic steatohepatitis in mice.

Link: MiP2023 Obergurgl AT

Stankova Pavla (2023)

Event: MiP2023 Obergurgl AT

Authors: Stankova Pavla, Peterova E, Dusek J, Elkalaf Moustafa, Cervinkova Zuzana, Kucera Otto

Introduction: In our previous study in a murine model of nonalcoholic steatohepatitis (NASH), we found reduced succinate-activated hepatic mitochondrial respiration and accumulation of succinate, a proinflammatory, profibrogenic, and oncogenic metabolite [1]. According to preliminary studies, telmisartan, an angiotensin II type 1 receptor blocker, positively affects insulin resistance and liver steatosis. This project aimed to investigate the effect of telmisartan on NASH in mice.
Methods: The NASH was induced in male mice fed a western-style diet (WD) for 36 weeks. During the last 6 weeks of the experiments, mice were administered daily telmisartan (oral gavage, 5 mg/kg b.w./day). Liver and epididymal fat histological changes were evaluated (Hematoxylin-eosin, Sirius red). Body parameters, plasma liver profile (VetScan), hepatic triglycerides, cholesterol, and the expression of selected proteins (WB/ELISA) and genes (qRT-PCR) were assessed. Mitochondrial respiration of liver homogenates was measured by high-resolution respirometry (OROBOROS Oxygraph-2k). Using Reporter Gene assay, telmisartan's activation of nuclear receptors was evaluated on HepG2 cells.
Results and discussion: Administration of telmisartan to mice fed a WD reduced absolute and relative liver weight and visceral adipose tissue weight, activities of ALT and AST, liver steatosis, and inflammation grade. These effects were accompanied by a significant increase in succinate-activated respiration in the ET state and the activity of succinate dehydrogenase. We confirmed that telmisartan is a PPAR-Ξ³ partial agonist and described the activating effect of telmisartan on the CAR receptor for the first time. Telmisartan appears to be a promising safety drug for treating NASH that affects metabolism at multiple levels.

  1. StaňkovÑ P, Kučera O, PeterovÑ E, Elkalaf M, Rychtrmoc D, Melek J, Podhola M, ZubÑňovÑ V, ČervinkovÑ Z (2021) Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model. https://doi.org/10.3390/ijms22136908

β€’ Keywords: NASH, Telmisartan, Succinate dehydrogenase, PPAR-Ξ³, CAR

β€’ O2k-Network Lab: CZ Hradec Kralove Cervinkova Z


Affiliations and acknowledgements

Stankova Pavla1, Peterova E1,2, Dusek J1, Elkalaf M1, Cervinkova Z1, Kucera O1
  1. Dept of Physiology, Fac of Medicine in Hradec Kralove, Charles Univ, Czech Republic
  2. Dept of Medical Biochemistry, Fac of Medicine in Hradec Kralove, Charles Univ, Czech Republic
Corresponding author: stankovap@lfhk.cuni.cz
Funding: This work was supported by InoMed project CZ.02.1.01/0.0/0.0/18_069/0010046 co-funded by the EU.


Labels:


Organism: Mouse  Tissue;cell: Liver  Preparation: Homogenate 



HRR: Oxygraph-2k  Event: Oral 


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