HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD)
Alessia Di Costanzo,
Annalisa Ronca,
Laura D’Erasmo,
Matteo Manfredini,
Francesco Baratta,
Daniele Pastori,
Michele Di Martino,
Fabrizio Ceci,
Francesco Angelico,
Maria Del Ben,
Chiara Pavanello,
Marta Turri,
Laura Calabresi,
Elda Favari,
Marcello Arca
Affiliations
Alessia Di Costanzo
Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy
Annalisa Ronca
Department of Food and Drug, University of Parma, 43124 Parma, Italy
Laura D’Erasmo
Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy
Matteo Manfredini
Department of Chemistry, Life Science, and Environmental Sustainability, University of Parma, 43124 Parma, Italy
Francesco Baratta
Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Daniele Pastori
Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Michele Di Martino
Department of Diagnostic of Radiological, Oncological and Anatomopathological Sciences, Sapienza University of Rome, 00161 Rome, Italy
Fabrizio Ceci
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
Francesco Angelico
Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy
Maria Del Ben
Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy
Chiara Pavanello
Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy
Marta Turri
Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy
Laura Calabresi
Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milan, Italy
Elda Favari
Department of Food and Drug, University of Parma, 43124 Parma, Italy
Marcello Arca
Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy
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 p p 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.
