Key result
Metabolic NAFLD is linked to ~19% lower cholesterol efflux capacity than genetic NAFLD.
Why the study?
Non-alcoholic fatty liver disease increases atherosclerosis risk, which may differ between metabolically- and genetically-driven NAFLD, but differences in HDL-mediated cholesterol efflux and plasma loading capacity were unclear.
Does metabolically-driven NAFLD alter HDL-mediated cholesterol efflux and plasma loading capacity compared to genetically-driven NAFLD and healthy controls?
Observational (n=39)
Yes
Does metabolically-driven NAFLD alter HDL-mediated cholesterol efflux and plasma loading capacity compared to genetically-driven NAFLD and healthy controls?
Metabolically-driven NAFLD, but not genetically-driven NAFLD, is associated with dysfunctional HDL-mediated cholesterol efflux and abnormal plasma loading capacity, suggesting impaired anti-atherogenic protection.
Answers are grounded in this paper and cite their sources.
Metabolic NAFLD may impair CEC and raise CLC unlike genetic forms; leaves open differential ASCVD mechanisms in small observational data.
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.
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Costanzo et al. (2020) conducted an observational in Non-Alcoholic Fatty Liver Disease (NAFLD) (n=39). Metabolically-driven NAFLD vs. Genetically-driven NAFLD and healthy controls was evaluated on Total HDL-mediated cholesterol efflux capacity (CEC) (-18.6%, p=<0.001). Metabolically-driven NAFLD, but not genetically-driven NAFLD, was associated with an 18.6% reduction in total HDL-mediated cholesterol efflux capacity compared to genetic NAFLD (p<0.001).
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