ArticleNutrition & metabolism2025
3-Hydroxybutyrate, a metabolite in sustaining neuronal cell vitality: a mendelian randomization and in vitro experimentation.
Article in Nutrition & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
- Elevated mitochondrial DNA copy number in euthyroid individuals with impaired peripheral sensitivity to thyroid hormones.Frontiers in endocrinology · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
backgroundRecent research has implicated mitochondrial DNA copy number (mtDNA-CN) and Tau protein levels in the blood as potential biomarkers for early Alzheimer's disease (AD) risk assessment, correlating with metabolite profiles. However, intermediary metabolites mediating these associations remain elusive.
methodsEmploying a two-sample and a mediation Mendelian randomization (MR) analysis of the IEU OpenGWAS database, involving 383,476 participants from a genome-wide association study (GWAS) and an exome-wide association study (ExWAS), we identified intermediary metabolites linking mtDNA-CN and Tau.Meanwhile, the effects of mediating metabolites on HT22 cell viability and its mitochondrial morphology were also assessed in conjunction with in vitro experiments.
resultsOur study revealed an association of mtDNA-CN on Tau (OR = 3.102, 95% CI: 1.016-9.472, P = 0.047), as well as on other 31 metabolites such as 3-Hydroxybutyrate (3HB), Docosahexaenoic acid (DHA), Acetate, Albumin, Apolipoprotein A-I (APOA1), and so on. Notably, 3HB was further implicated in a relationship with Tau (OR = 6.030, 95% CI: 1.054-34.491, P = 0.043), acting as a mediator between mtDNA-CN and Tau. In vitro experiments demonstrated that 3HB positively sustained HT22 cell viability by MTT assay and mitigated mitochondrial swelling under low glucose conditions, as observed via HIS-SIM. In Western blot (WB) and quantitative real-time PCR (qPCR) assays, phosphorylation levels of Tau at serine 262 (p-Tau262) and serine 396 (p-Tau396) were tended to decline following 3HB intervention. Additionally, a positive correlation was identified between 3HB concentration and mtDNA-CN.
conclusionsThese findings underscore the potential of 3HB as a biomarker and mediator in early AD risk assessment. Moreover, 3HB's ability to enhance cell viability, maintain mitochondrial morphology, decrease phosphorylated Tau protein expression and increase mtDNA-CN under stressful conditions, suggesting its therapeutic potential in improving the imbalance of energy metabolism in the AD brain.
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