Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may dier 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 dier 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 dffusion; 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.

HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD) / Di Costanzo, Alessia; Ronca, Annalisa; D’Erasmo, Laura; Manfredini, Matteo; Baratta, Francesco; Pastori, Daniele; Di Martino, Michele; Ceci, Fabrizio; Angelico, Francesco; Del Ben, Maria; Pavanello, Chiara; Turri, Marta; Calabresi, Laura; Favari, Elda; Arca, Marcello. - In: BIOMEDICINES. - ISSN 2227-9059. - 8:12(2020), p. 625. [10.3390/biomedicines8120625]

HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD)

Ronca, Annalisa;Manfredini, Matteo;Favari, Elda;
2020

Abstract

Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may dier 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 dier 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 dffusion; 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.
HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD) / Di Costanzo, Alessia; Ronca, Annalisa; D’Erasmo, Laura; Manfredini, Matteo; Baratta, Francesco; Pastori, Daniele; Di Martino, Michele; Ceci, Fabrizio; Angelico, Francesco; Del Ben, Maria; Pavanello, Chiara; Turri, Marta; Calabresi, Laura; Favari, Elda; Arca, Marcello. - In: BIOMEDICINES. - ISSN 2227-9059. - 8:12(2020), p. 625. [10.3390/biomedicines8120625]
File in questo prodotto:
File Dimensione Formato  
biomedicines-08-00625.pdf

accesso aperto

Tipologia: Versione (PDF) editoriale
Licenza: Creative commons
Dimensione 1.99 MB
Formato Adobe PDF
1.99 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2885535
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 10
social impact