Thématique

Transversal Research

Responsable : Clarisse Vandebrouck

 

Within STIM laboratory, the discovery that Cystic Fibrosis cells were lipointoxicated led to opening a new field of research and to patents which then permitted the creation in 2016 of a Spin-off by Dr Thierry Ferreira (Conic Meds). Conic Meds and STIM then created the cooperative laboratory « Lipointoxication and Channelopathies » LitCh that developed its R&D in particular with previous TIRC and TIME teams on cardiopathies and cystic fibrosis. Four scientists belonging to STIM laboratory devoted part of their work time to LitCh laboratory activity, including Clarisse Vandebrouck who has becoming the head of this cooperative laboratory.

In the approach of the PRéTI laboratory, the cooperative laboratory LitCh has been transformed into a global approach aiming at developping transversal research between the different axes.

Lipointoxication of various cellular models remains of high interest in this context.

Lipointoxications are characterized by an accumulation of saturated fatty acids in the membranes of the cells of our organism, which affects their proper functioning. The targeted diseases include obstructive respiratory diseases, such as Cystic Fibrosis and Chronic Obstructive Pulmonary Diseases (COPD), but also metabolic syndromes, responsible for Type 2 Diabetes, Hepatic Steatosis and certain cardiovascular diseases.

In the context of the new partnership with PRéTI, we continue the study of lipointoxication in connection with the models of investigations and pathologies studied by the PRéTI laboratory. Thus lipointoxication is addressed i) in cystic fibrosis and we have shown that human bronchial epithelial cells extracted from lungs of patients with Obstructive Pulmonary Diseases (OPDs), i. e. Cystic Fibrosis (CF) individuals and Smokers, display a characteristic lipointoxication signature, with excessive amounts of saturated phospholipids (PLs). Moreover, we have recently made an update on lipointoxication in cystic fibrosis in order to make a complete inventory of the subject; ii) in metabolic diseases and we have shown that fatty acids from the diet can redistribute within PLs in a very selective manner, with phosphatidylcholine being the preferred sink for this redistribution. Moreover, in the High-fat/high-fructose rat model, most organs are protected from this redistribution, at the expense of the liver and skeletal muscles. Interestingly, such a redistribution correlates with clear-cut alterations in the function of these organs (Bacle et al., DMM 2020) ; iii) in muscle where we have postulated that PolyUnsaturated Fatty Acids (PUFA)-containing PLs could be central players for muscle cell adaptation to mechanical constraints. By a combination of in cellulo and in silico approaches, we have shown that PUFA, and particularly the ω-3 DocosaHexaenoic Acid (DHA), regulates important properties of the plasma membrane that improve muscle cell resilience to mechanical constraints. Thanks to their unique property to contortionate within the bilayer plane, they facilitate the formation of Vacuole-like dilation (VLD) which, in turn, reduce membrane stress and avoid cell breakage under mechanical constraints.

We will continue our joint research on lipo-intoxication in accordance with the three models of the PRéTI laboratory.

Valorisation scientifique

  • 12

    Publications

  • 2

    Brevets

  • 1

    Chapitre de Livre

Publications / Brevets

PUBLICATIONS

2022

Florian Jacquot, Spiro Khoury, Bonnie Labrum, Kévin Delanoe, Ludivine Pidoux, Julie Barbier, Lauriane Delay, Agathe Bayle, Youssef Aissouni, David A. Barriere, Kim Kultima, Eva Freyhult, Anders Hugo, Eva Kosek, Aisha S. Ahmed, Alexandra Jurczak, Eric Lingueglia, Camilla I. Svensson, Véronique Breuil, Thierry Ferreira, Fabien Marchand, Emmanuel Deval (2021). Lysophosphatidyl-choline 16:0 mediates persistent joint pain through Acid-Sensing Ion Channel 3: preclinical and clinical evidences. Pain 2022 Jan 27. https://doi.org/10.1097/j.pain.0000000000002596 (IF 6,961)

2021

Alexandra Jurczak; Lauriane Delay; Julie Barbier; Nils Simon; Emerson Krock; Katalin Sandor; Nilesh Mohan Agalave; Resti Rudjito; Gustaf Wigerblad; Katarzyna Rogóż; Arnaud Briat; Elisabeth Miot-Noirault; Arisai Martinez-Martinez; Dieter Brömme; Caroline Grönwall; Vivianne Malmström; Lars Klareskog; Spiro Khoury; Thierry Ferreira; Bonnie Labrum; Emmanuel Deval; Juan Miguel Jiménez-Andrade; Fabien Marchand; Camilla I. Svensson (2021). Antibody-induced pain-like behavior and bone erosion – links to subclinical inflammation, osteoclast activity and ASIC3-dependent sensitization. Pain https://doi.org/10.1097/j.pain.0000000000002543 (IF 6,961)

Bacle A, Kadri L, Khoury S, Vandebrouck C, Bescond, Faivre JF, Ferreira T and Sebille S. (2021) Polyunsaturated phospholipids increase cell resilience to mechanical constraints. Cells 2021, 10, 937. https://doi.org/10.3390/cells10040937 (IF=4.366)

2020

Vandebrouck C and Ferreira T. (2020) Glued in lipids: lipointoxicity in Cystic Fibrosis. EBioMedicine 6: doi.org/10.1016/j.ebiom.2020.103038 (IF= 6.490)

Bacle A, Kadri L, Khoury S, Cognard C, Ferru-Clément R, Faivre JF, Bescond J, Krzesiak A, Delpech N, Colas J, Vandebrouck C, Sébille S and Ferreira T. (2020). A comprehensive study of Phospholipid fatty acid remodeling in the early onset of the metabolic syndrome: correlations to organ dysfunction. Disease models and mechanisms. Jun 15;13(6) : dmm043927. https://doi.org/10.1242/dmm.043927. (IF= 4.651)

2018

Kadri L, Ferru-Clément R, Bacle A, Payet LA, Cantereau A, Hélye R, Becq F, Jayle C, Vandebrouck C, Ferreira T. Modulation of cellular membrane properties as a potential therapeutic strategy to counter lipointoxication in obstructive pulmonary diseases. Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt B):3069-3084. (IF=5.476)

2016

Ferru-Clément R, Spanova M, Dhayal S, Morgan NG, Hélye R, Becq F, Hirose H, Antonny B, Vamparys L, Fuchs PF, Ferreira T. Targeting surface voids to counter membrane disorders in lipointoxication-related diseases. J Cell Sci. 2016 Jun 15;129(12):2368-81. (IF=4,517)

Marra S, Ferru-Clément R, Breuil V, Delaunay A, Christin M, Friend V, Sebille S, Cognard C, Ferreira T, Roux C, Euller-Ziegler L, Noel J, Lingueglia E, Deval E. Non-acidic activation of pain-related Acid-Sensing Ion Channel 3 by lipids. EMBO J. 2016 Feb 15;35(4):414-28. (IF=11,2)

 2015

Antonny B, Vanni S, Shindou H, Ferreira T. From zero to six double bonds: phospholipid unsaturation and organelle function. Trends Cell Biol. 2015 Jul;25(7):427-36. doi: 10.1016/j.tcb.2015.03.004. Epub 2015 Apr 20.

2014

Payet LA, Kadri L, Giraud S, Norez C, Berjeaud JM, Jayle C, Mirval S, Becq F, Vandebrouck C, Ferreira T. Cystic fibrosis bronchial epithelial cells are lipointoxicated by membrane palmitate accumulation. PLoS One. 2014 Feb 19;9(2):e89044. (IF=3.73)

Pinot M, Vanni S, Pagnotta S, Lacas-Gervais S, Payet LA, Ferreira T, Gautier R, Goud B, Antonny B, Barelli H. Lipid cell biology. Polyunsaturated phospholipids facilitate membrane deformation and fission by endocytic proteins. Science. 2014 Aug 8;345(6197):693-7. doi: 10.1126/science.1255288.

2013

Payet LA, Pineau L, Snyder EC, Colas J, Moussa A, Vannier B, Bigay J, Clarhaut J, Becq F, Berjeaud JM, Vandebrouck C, Ferreira T. Saturated fatty acids alter

CHAPITRE DE LIVRE

2018

Bacle A & Ferreira T. Strategies to Counter Saturated Fatty Acid (SFA)-Mediated Lipointoxication. November 2018 DOI: 10.1016/B978-0-12-811297-7.00027-5. In book: The Molecular Nutrition of Fats. Publisher: Elsevier

BREVETS

Ferreira T, Ferru-Clément R & Vandebrouck C. Compounds, compositions and uses thereof for the prevention and/or treatment of dyslipidemia. Patent: WO 2015052237 A1; PCT/EP2014/071543

Ferreira T, Spanova M, Ferru-Clément R, Dhaval S & Morgan NG. Compounds and compositions comprising such compounds for the prevention or treatment of dyslipidaemias. Patent: WO 2015052433 A1