Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Trodusquemine (MSI-1436) restores metabolic flexibility and mitochondrial dynamics in insulin-resistant equine hepatic progenitor cells (HPCs)

Badr Qasem
ORCID logo ,
Lynda Bourebaba
ORCID logo ,
Agnieszka Dąbrowska
ORCID logo ,
Jarosław Króliczewski
,
Jacek Łyczko
ORCID logo ,
Krzysztof Marycz
*
Version 1 : Received: 4 July 2023 / Approved: 5 July 2023 / Online: 5 July 2023 (12:21:07 CEST)

A peer-reviewed article of this Preprint also exists.

Qasem, B.; Dąbrowska, A.; Króliczewski, J.; Łyczko, J.; Marycz, K. Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs). Cells 2024, 13, 152, doi:10.3390/cells13020152. Qasem, B.; Dąbrowska, A.; Króliczewski, J.; Łyczko, J.; Marycz, K. Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs). Cells 2024, 13, 152, doi:10.3390/cells13020152.

Abstract

Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine worldwide, and there is growing interest in utilizing molecular agents for modulation of hepatocyte function for potential clinical applications with recent studies showing promising results in the inhibition of PTP1B on adipose-derived stromal cells. In this study, we investigated the effects of MSI-1436 on equine hepatic progenitor cells (HPCs) in terms of their proliferative activity, glucose uptake, and mitochondrial morphogenesis under lipotoxic condition. Our study found that MSI-1436 promotes the entry of HPCs in the cell cycle and rescues them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the morphological architecture of the cells. Additionally, our findings suggest that MSI-1436 enhances the 2-NBDG internalization by increasing the expression of SIRT1, which is associated with liver insulin sensitivity, and promotes mitochondrial dynamics by modulating their number and morphotype through PINK1, MFN1, and MFN2 increased expression. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in the treatment of EMS and insulin dysregulation.

Keywords

MSI-1436; Eq_HPCs; glucose uptake; palmitate; mitochondrial dynamics/mitophagy

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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