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Front. Endocrinol. | doi: 10.3389/fendo.2019.00726

Induction of Stearoyl-CoA 9-desaturase 1 protects human mesenchymal stromal cells against palmitic acid-induced lipotoxicity and inflammation.

 Antoine Dalla Valle1,  Pascale Vertongen1,  Delphine Spruyt1, Jessica Lechanteur1, Valérie Suain1,  Nathalie Gaspard1, jean-pierre Brion1, Valérie Gangji1 and Joanne Rasschaert1*
  • 1Université libre de Bruxelles, Belgium

In bone diseases such as osteonecrosis and osteoporosis, a shift toward a preferential differentiation of mesenchymal stromal cells (MSCs) into adipocytes at the expense of the osteoblastic lineage is described, leading to excessive accumulation of adipocytes in the bone marrow of the patients. The influence of cytokines and adipokines secreted by adipocytes on skeletal health is already well documented but the impact of free fatty acids release on bone cell biology and viability is an emerging concept. We have previously demonstrated that the saturated fatty acid (SFA) palmitate (Palm) is cytotoxic for human MSCs (hMSCs) and osteoblasts whereas oleate (Ole), a monounsaturated fatty acid (MUFA), has no toxic effect. Moreover, Ole protects cells against lipotoxicity. Our observations led us to propose that the toxicity of the SFA is not correlated to its intracellular accumulation but could rather be related to the intracellular SFA/MUFA ratio, which finally determines the toxic effect of SFA. Therefore, in the present study, we have investigated the potential protective role of the enzyme stearoyl-CoA 9-desaturase 1 (SCD1) against the deleterious effects of Palm. SCD1 is an enzyme responsible for desaturation of SFA to MUFA; its activation could therefore lead to modifications of the intracellular SFA/MUFA ratio. In the present study, we showed that hMSC express SCD1 and liver X receptors (LXRs), transcription factors regulating SCD1 expression. Human MSCs (hMSCs) treatment with a LXRs agonist triggered SCD1 expression and drastically reduced Palm-induced cell mortality, caspases 3/7 activation, endoplasmic reticulum stress and inflammation induced by Palm. We also observed that, in the presence of Palm, the LXRs agonist induced provoked lipid droplets formation, augmented the total cellular neutral lipid content but decreased the SFA/MUFA ratio when compared to Palm treatment alone. Addition of an inhibitor of SCD1 activity abrogated the positive effects of the LXRs agonist, suggesting that SCD1 could play a key role in protecting human MSCs against lipotoxicity.

Keywords: human mesenchymal stromal cells (hMSC), Fatty Acids, lipotoxicity, er stress, Inflammation, liver X receptor activator, Stearoyl-CoA 9-desaturase 1 (SCD1), Bone Diseases

Received: 09 May 2019; Accepted: 09 Oct 2019.

Copyright: © 2019 Dalla Valle, Vertongen, Spruyt, Lechanteur, Suain, Gaspard, Brion, Gangji and Rasschaert. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Joanne Rasschaert, Université libre de Bruxelles, Brussels, Belgium, joanne.rasschaert@ulb.ac.be