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HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD)
- Source :
- Biomedicines, Vol 8, Iss 625, p 625 (2020), Biomedicines, Volume 8, Issue 12
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
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 (&minus<br />18.6%<br />p &lt<br />0.001) as well as that mediated by cholesterol transporters (&minus<br />25.3% ABCA1<br />&minus<br />16.3% ABCG1<br />14.8% aqueous diffusion<br />all p &lt<br />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 &lt<br />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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Medicine (miscellaneous)
030204 cardiovascular system & hematology
reverse cholesterol transport (RCT)
digestive system
genetic NAFLD
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
lcsh:QH301-705.5
biology
urogenital system
Cholesterol
Fatty liver
nutritional and metabolic diseases
medicine.disease
digestive system diseases
metabolic NAFLD
030104 developmental biology
Endocrinology
lcsh:Biology (General)
ABCG1
chemistry
cholesterol efflux capacity (CEC)
cholesterol loading capacity (CLC)
ABCA1
cardiovascular system
biology.protein
Efflux
Metabolic syndrome
Ex vivo
Lipoprotein
Subjects
Details
- ISSN :
- 22279059
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Biomedicines
- Accession number :
- edsair.doi.dedup.....9d0927ab6b78d9b1d97e7c97d8b02bc5