Peripheral blood mitochondrial DNA copy number, a potential marker of non‐alcoholic fatty liver disease?

Abstract

IntroductionNonalcoholic fatty liver disease (NAFLD) includes a spectrum of histological findings ranging from simple steatosis (SS) to non‐alcoholic steatohepatitis (NASH). Although often considered the hepatic manifestation of metabolic syndrome (MS), longitudinal studies suggest that NAFLD precedes MS. To date, liver biopsy is the most accurate method to differentiate between SS and NASH. However, recent studies indicate an association between mitochondrial DNA (mtDNA) copy number and NAFLD severity in liver biopsies. If a similar association exists in peripheral blood, mtDNA copy number could represent a non‐invasive alternative for differentiating NAFLD disease stages.Given the above, we analyzed whether mtDNA copy number differs in individuals discordant for NAFLD and MS. We also probed for correlations between liver and peripheral blood mtDNA copy number, in addition to associations between NAFLD and mtDNA copy number.ObjectiveTo analyze whether mtDNA copy number is a useful blood‐based marker of NAFLD severity.Materials and methodsCohort = 73 peripheral blood samples and liver biopsies obtained from patients that were operated for gallstones; individuals were separated into 4 groups: controls (n = 27), NAFLD (n = 14), MS (n = 9) and MS + NAFLD (n = 23). NAFLD severity was determined according to the parameters described by Kleiner; mtDNA copy number was determined by semiquantitative PCR.ResultsWe found no significant differences in mtDNA copy number across the four groups analyzed (i.e. control, NAFLD, MS, MS+NAFLD). However, we did find an association between mtDNA copy number and NAFLD severity. In particular, we found that a significant increase in mtDNA copy number in SS relative to control samples, while mtDNA copy number was significantly reduced in NASH relative to SS.ConclusionAkin to the previously published data of mtDNA copy number in liver biopsies of individuals with NAFLD, we uncovered a dynamic relationship between mtDNA copy number and NAFLD severity in peripheral blood samples. This suggests that mtDNA copy number may be a promising blood‐based biomarker for differentiating between SS and NASH. To address this issue, we are currently probing for correlations between liver and peripheral blood mtDNA copy number.Support or Funding InformationMexican National Council for Science and Technology (CONACyT).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Investigation of FGF21 mRNA levels and relative mitochondrial DNA copy number levels and their relation in nonalcoholic fatty liver disease: a case-control study

“…This can have several reasons, for example, beside limited number of samples, our studies had a case-control design and we did not investigate liver mtDNA-CN in individuals through long duration of time. Also, evidence indicated that mtDNA-CN can vary between different cell types and answer differently to various physiologic and pathologic states including NAFLD ( Tapia et al, 2018 ; Ma et al, 2020 ; Filograna et al, 2021 ) suggesting a dynamic nature for this parameter.…”