Within the PRéTI laboratory, we have developed a transversal axis which currently includes two main themes:
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.
B) Energy metabolism
The study of energy metabolism is the main focus of our research activities. As mitochondria play a major role in cellular energetics, we are particularly interested in the study of mitochondrial functions as well as in the understanding of the regulations of mitochondrial life cycle (mitochondrial biogenesis, mitochondrial dynamics and mitophagy). Within the PRéTI laboratory, our objective is to develop tools for the systematic study of energy metabolism in the study models of the laboratory. We plan to develop methods to analyze the energy metabolism of epithelial cells in order to study the possible impact of Trikafta® treatment on the mitochondrial alterations described in cystic fibrosis. Dr Piquereau will also offer his expertise in the study of the energy metabolism of the heart and skeletal muscle to help better understand the role of mitophagy in Duchenne muscular dystrophy and the alterations of the metabolism of cardiac fibroblasts in the context of lipointoxication. Ultimately, the idea is to develop an axis consisting in studying cellular energy metabolism that each member of the laboratory will be able to resort, in order to go further in the understanding of his respective study model.
Chapitre de Livre
Publications / Brevets
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 (2022). Antibody-induced pain-like behavior and bone erosion – links to subclinical inflammation, osteoclast activity and ASIC3-dependent sensitization. Pain. 2022 Aug 1;163(8):1542-1559. doi: 10.1097/j.pain.0000000000002543 (IF 6,961)
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)
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)
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)
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.
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.
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
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
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