Alessia Di Costanzo1, Annalisa Ronca2, Laura D'Erasmo1, Matteo Manfredini3, Francesco Baratta4, Daniele Pastori4, Michele Di Martino5, Fabrizio Ceci6, Francesco Angelico7, Maria Del Ben4, Chiara Pavanello8, Marta Turri8, Laura Calabresi8, Elda Favari2, Marcello Arca1. 1. Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy. 2. Department of Food and Drug, University of Parma, 43124 Parma, Italy. 3. Department of Chemistry, Life Science, and Environmental Sustainability, University of Parma, 43124 Parma, Italy. 4. Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy. 5. Department of Diagnostic of Radiological, Oncological and Anatomopathological Sciences, Sapienza University of Rome, 00161 Rome, Italy. 6. Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy. 7. Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy. 8. Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy.
Abstract
Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically- vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically- vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148M PNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (-18.6%; p < 0.001) as well as that mediated by cholesterol transporters (-25.3% ABCA1; -16.3% ABCG1; -14.8% aqueous diffusion; all p < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p < 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired.
Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically- vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically- vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148MPNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (-18.6%; p < 0.001) as well as that mediated by cholesterol transporters (-25.3% ABCA1; -16.3% ABCG1; -14.8% aqueous diffusion; all p < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p < 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired.
Authors: Giuseppe Mandraffino; Carmela Morace; Maria Stella Franzè; Veronica Nassisi; Davide Sinicropi; Maria Cinquegrani; Carlo Saitta; Riccardo Scoglio; Sebastiano Marino; Alessandra Belvedere; Valentina Cairo; Alberto Lo Gullo; Michele Scuruchi; Giovanni Raimondo; Giovanni Squadrito Journal: Biomedicines Date: 2022-07-22
Authors: George Athanasios Karpouzas; Bianca Papotti; Sarah Ormseth; Marcella Palumbo; Elizabeth Hernandez; Maria Pia Adorni; Francesca Zimetti; Matthew Budoff; Nicoletta Ronda Journal: RMD Open Date: 2022-09
Authors: Francesco Baratta; Laura D'Erasmo; Alessia Di Costanzo; Ilaria Umbro; Daniele Pastori; Francesco Angelico; Maria Del Ben Journal: Biomedicines Date: 2022-03-19