[en] Abstract: (1) Background: Obesity and type 2 diabetes have been suspected to impact both intrin-sic metabolism and function of circulating immune cells. (2) Methods: To further investigate this immunometabolic modulation, we profiled the phospholipidome of the peripheral blood mononu-clear cells (PBMCs) in lean, normoglycemic obese (OBNG) and obese with dysglycemia (OBDysG) individuals. (3) Results: The global PBMCs phospholipidome is significantly downmodulated in OBDysG unlike OBNG patients when compared to lean ones. Multiple linear regression analyses show a strong negative relationship between the global PBMCs phospholipidome and parameters assessing insulin resistance. Even though all classes of phospholipid are affected, the relative abundance of each class is maintained with the exception of Lyso-PC/PC and Lyso-PE/PE ratios that are downmodulated in PBMCs of OBDysG compared to OBNG individuals. Interestingly, the percentage of saturated PC is positively associated with glycated hemoglobin (HbA1c). Moreover, a few lipid species are significantly downmodulated in PBMCs of OBDysG compared to OBNG individuals, making possible to distinguish the two phenotypes. (4) Conclusions: This lipidomic study highlights for the first-time modulations of the PBMCs phospholipidome in obese patients with prediabetes and type 2 diabetes. Such phospholipidome remodeling could disrupt the cell membranes and the lipid mediator’s levels, driving an immune cell dysfunction.
Research Center/Unit :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Wilkin, Chloé ; Université de Liège - ULiège > GIGA I3 - Immunometabolism and Nutrition
Colonval, Megan; Université de Liège - ULiège > GIGA I3 - Immunometabolism and Nutrition
Dehairs, Jonas; KU Leuven > Department of Oncology > Laboratory of Lipid Metabolism and Cancer
Esser, Nathalie ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de diabétologie, nutrition, maladies métaboliques
Iovino, Margaud ; Université de Liège - ULiège > GIGA I3 - Immunometabolism and Nutrition
Gianfrancesco, Marco A.; Université de Liège - ULiège > GIGA I3 - Immunometabolism and Nutrition
FADEUR, Marjorie ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de diabétologie, nutrition, maladies métaboliques
Swinnen, Johan V.; KU Leuven > Department of Oncology > Laboratory of Lipid Metabolism and Cancer
PAQUOT, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de diabétologie, nutrition, maladies métaboliques
Piette, Jacques ; Université de Liège - ULiège > GIGA I3 - Virology and Immunology
Legrand, Sylvie ; Université de Liège - ULiège > GIGA I3 - Immunometabolism and Nutrition
Language :
English
Title :
New insights on the PBMCs phospholipidome in obesity demonstrate modulations associated with insulin resistance and glycemic status
Publication date :
29 September 2021
Journal title :
Nutrients
ISSN :
2072-6643
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
Esser, N.; L’homme, L.; De Roover, A.; Kohnen, L.; Scheen, A.J.; Moutschen, M.; Piette, J.; Legrand-Poels, S.; Paquot, N. Obesity phenotype is related to NLRP3 inflammasome activityand immunological profile of visceral adipose tissue. Diabetologia 2013, 56, 2487–2497. [CrossRef]
Hildreth, A.D.; Ma, F.; Wong, Y.Y.; Sun, R.; Pellegrini, M.; O’Sullivan, T.E. Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nat. Immunol. 2021, 22, 639–653. [CrossRef] [PubMed]
Andersen, C.J.; Murphy, K.E.; Fernandez, M.L. Impact of Obesity and Metabolic Syndrome on Immunity. Adv. Nutr. 2016, 7, 66–75. [CrossRef] [PubMed]
Bandaru, P.; Rajkumar, H.; Nappanveettil, G. Altered or impaired immune response upon vaccination in WNIN/Ob rats. Vaccine 2011, 29, 3038–3042. [CrossRef] [PubMed]
Sheridan, P.A.; Paich, H.A.; Handy, J.; Karlsson, E.A.; Hudgens, M.G.; Sammon, A.B.; Holland, L.A.; Weir, S.; Noah, L.; Beck, M.A. Obesity is associated with impaired immune response to influenza vaccination in humans. Int. J. Obes. 2012, 36, 1072–1077. [CrossRef]
Calle, E.E.; Kaaks, R. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat. Rev. Cancer 2004, 4, 579–591. [CrossRef]
Renehan, A.G.; Tyson, M.; Egger, M.; Heller, R.F.; Zwahlen, M. Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Lancet 2008, 371, 569–578. [CrossRef]
Falagas, M.E.; Kompoti, M. Obesity and infection. Lancet. Infect. Dis. 2006, 6, 438–446. [CrossRef]
O’Neill, L.A.J.; Kishton, R.J.; Rathmell, J. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 2016, 16, 553–565. [CrossRef] [PubMed]
Castoldi, A.; Monteiro, L.B.; van Teijlingen Bakker, N.; Sanin, D.E.; Nisha Rana, N.; Corrado, M.; Cameron, A.M.; Hässler, F.; Matsushita, M.; Caputa, G.; et al. Triacylglycerol synthesis enhances macrophage inflammatory function. Nat. Commun. 2020, 11, 4107. [CrossRef]
Nathan, L.; Wonhwa, C. Phosphatidylserine binding is essential for plasma membrane recruitment and signaling function of 3-phosphoinositide-dependent kinase-1. J. Biol. Chem. 2011, 286, 41265–41272.
Grzelczyk, A.; Gendaszewska-Darmach, E. Novel bioactive glycerol-based lysophospholipids: New data—New insight into their function. Biochimie 2013, 95, 667–679. [CrossRef]
Sen, P.; Dickens, A.M.; López-Bascón, M.A.; Lindeman, T.; Kemppainen, E.; Lamichhane, S.; Rönkkö, T.; Ilonen, J.; Toppari, J.; Veijola, R.; et al. Metabolic alterations in immune cells associate with progression to type 1 diabetes. Diabetologia 2020, 63, 1017–1031. [CrossRef]
Weir, J.M.; Wong, G.; Barlow, C.K.; Greeve, M.A.; Kowalczyk, A.; Almasy, L.; Comuzzie, A.G.; Mahaney, M.C.; Jowett, J.B.M.; Shaw, J.; et al. Plasma lipid profiling in a large population-based cohort. J. Lipid Res. 2013, 54, 2898–2908. [CrossRef]
Meikle, P.J.; Wong, G.; Barlow, C.K.; Weir, J.M.; Greeve, M.A.; MacIntosh, G.L.; Almasy, L.; Comuzzie, A.G.; Mahaney, M.C.; Kowalczyk, A.; et al. Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes. PLoS ONE 2013, 8, e74341. [CrossRef]
Razquin, C.; Toledo, E.; Clish, C.B.; Ruiz-Canela, M.; Dennis, C.; Corella, D.; Papandreou, C.; Ros, E.; Estruch, R.; Guasch-Ferré, M.; et al. Plasma Lipidomic Profiling and Risk of Type 2 Diabetes in the PREDIMED Trial. Diabetes Care 2018, 41, 2617–2624. [CrossRef] [PubMed]
American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes. Diabetes Care 2020, 43, S14–S31. [CrossRef] [PubMed]
Liebisch, G.; Lieser, B.; Rathenberg, J.; Drobnik, W.; Schmitz, G. High-throughput quantification of phosphatidylcholine and sphingomyelin by electrospray ionization tandem mass spectrometry coupled with isotope correction algorithm. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2004, 1686, 108–117. [CrossRef] [PubMed]
Huynh, K.; Barlow, C.K.; Jayawardana, K.S.; Weir, J.M.; Mellett, N.A.; Cinel, M.; Magliano, D.J.; Shaw, J.E.; Drew, B.G.; Meikle, P.J. High-Throughput Plasma Lipidomics: Detailed Mapping of the Associations with Cardiometabolic Risk Factors. Cell Chem. Biol. 2019, 26, 71–84. [CrossRef] [PubMed]
Gianfrancesco, M.A.; Dehairs, J.; L’homme, L.; Herinckx, G.; Esser, N.; Jansen, O.; Habraken, Y.; Lassence, C.; Swinnen, J.V.; Rider, M.H.; et al. Saturated fatty acids induce NLRP3 activation in human macrophages through K+ efflux resulting from phospholipid saturation and Na, K-ATPase disruption. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2019, 1864, 1017–1030. [CrossRef]
Pilon, M. Revisiting the membrane-centric view of diabetes. Lipids Health Dis. 2016, 15, 167. [CrossRef]
Varshney, P.; Yadav, V.; Saini, N. Lipid rafts in immune signalling: Current progress and future perspective. Immunology 2016, 149, 13–24. [CrossRef]
Soriguer, F.; García-Serrano, S.; García-Almeida, J.M.; Garrido-Sánchez, L.; García-Arnés, J.; Tinahones, F.J.; Cardona, I.; Rivas-Marín, J.; Gallego-Perales, J.L.; García-Fuentes, E. Changes in the serum composition of free-fatty acids during an intravenous glucose tolerance test. Obesity 2009, 17, 10–15. [CrossRef] [PubMed]
Foretz, M.; Guigas, B.; Viollet, B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat. Rev. Endocrinol. 2019, 15, 569–589. [CrossRef] [PubMed]
Boudaba, N.; Marion, A.; Huet, C.; Pierre, R.; Viollet, B.; Foretz, M. AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not Promote Fatty Liver Development. EBioMedicine 2018, 28, 194–209. [CrossRef] [PubMed]
