β-hydroxybutyrate and mitochondria mediate the association between medium-chain fatty acids, DHA and mild cognitive
Tong Yang1,2,3, Huilian Duan2,3,4, Yuan Li2,3,4
1Department of Epidemiology & Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, People's Republic of China.
Background:
Medium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) could affect the occurrence of mild cognitive impairment (MCI). β-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn) and mitochondrial DNA (mtDNA) deletions might be their potential mechanisms. This study aimed to explore the relationship between MCFAs, DHA and MCI, and potential mechanisms.
Methods:
This study used data from Tianjin Elderly Nutrition and Cognition (TENC) cohort study, 120 individuals were identified with new onset MCI during follow-up, 120 individuals without MCI were selected by 1:1 matching sex, age, and education levels as the control group from TENC. Conditional logistic regression analysis and mediation effect analysis were used to explore their relationship.
Results:
Higher serum octanoic acid levels (OR: 0.633, 95% CI: 0.520, 0.769), higher serum DHA levels (OR: 0.962, 95% CI: 0.942, 0.981), and more mtDNAcn (OR: 0.436, 95% CI: 0.240, 0.794) were associated with lower MCI risk, while more mtDNA deletions was associated with higher MCI risk (OR: 8.833, 95% CI: 3.909, 19.960). Mediation analysis suggested that BHB and mtDNAcn, in series, have mediation roles in the association between octanoic acid and MCI risk, and mtDNA deletions have mediation roles in the association between DHA and MCI risk.
Conclusion:
Higher serum octanoic acid and DHA levels were associated with lower MCI risk. Octanoic acid could affect the incidence of MCI through BHB, then mitochondria function, or through mitochondria function, or directly. Serum DHA level could affect the incidence of MCI through mitochondria function, or directly.
Insights
Higher levels of medium-chain fatty acids (MCFAs) like octanoic acid and docosahexaenoic acid (DHA) are linked to a reduced risk of mild cognitive impairment (MCI). These fatty acids may influence MCI through mechanisms involving beta-hydroxybutyrate (BHB) and mitochondrial function.
Area of Science:
- Nutritional Neuroscience
- Mitochondrial Biology
- Cognitive Aging Research
Background:
- Mild cognitive impairment (MCI) is a growing concern in aging populations.
- Medium-chain fatty acids (MCFAs) and docosahexaenoic acid (DHA) are dietary components with potential neuroprotective roles.
- Mechanisms involving beta-hydroxybutyrate (BHB), mitochondrial DNA copy number (mtDNAcn), and mitochondrial DNA (mtDNA) deletions are hypothesized to mediate these effects.
Purpose of the Study:
- To investigate the association between serum levels of MCFAs (specifically octanoic acid) and DHA with the risk of developing MCI.
- To explore the potential mediating roles of BHB, mtDNAcn, and mtDNA deletions in these relationships.
Main Methods:
- Analysis of data from the Tianjin Elderly Nutrition and Cognition (TENC) cohort study.
- Inclusion of 120 incident MCI cases and 120 matched controls.
- Application of conditional logistic regression and mediation effect analysis.
Main Results:
- Elevated serum octanoic acid and DHA levels were significantly associated with a lower risk of MCI.
- Higher mitochondrial DNA copy number (mtDNAcn) was linked to reduced MCI risk, whereas increased mtDNA deletions correlated with higher MCI risk.
- Mediation analysis indicated that BHB and mtDNAcn mediate the effect of octanoic acid on MCI risk, while mtDNA deletions mediate the effect of DHA.
Conclusions:
- Higher serum concentrations of octanoic acid and DHA are protective against MCI.
- The neuroprotective effects of octanoic acid may involve BHB and mitochondrial function.
- DHA's protective role against MCI appears to be mediated by mitochondrial function and/or mitochondrial DNA integrity.
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