ArticleJournal of cachexia, sarcopenia and muscle2025
Prepregnancy Obesity Reprograms Offspring Skeletal Muscle Fibre Transition Through H3K9me3.
Article in Journal of cachexia, sarcopenia and muscle, 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Mitochondrial Dysfunction: A Critical Link Between Maternal Diet and Offspring Metabolic Health.Biomolecules · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
backgroundMaternal prepregnancy obesity predisposes offspring to obesity and metabolic disorders, yet its impact on skeletal muscle fibre transition remains unclear. Given that skeletal muscle plays a crucial role in systemic metabolism, we investigated how maternal prepregnancy high-fat diet (HFD) influences muscle fibre composition and metabolic function in offspring.
methodsWe established mouse models with a prepregnancy chow diet (CD) and a prepregnancy high-fat diet (HFD) for 8 weeks to compare metabolic phenotypes in offspring. Skeletal muscles from offspring were analysed using RNA sequencing, quantitative reverse transcription polymerase chain reaction and western blot to understand the changes in metabolic and signalling pathways. siRNA knockdown and lentiviral-mediated overexpression experiments were conducted in vitro and in vivo to validate molecular mechanisms. Chromatin immunoprecipitation followed by qPCR (ChIP-qPCR) was used to assess histone modification levels at promoter regions.
resultsMale and female offspring of prepregnancy obese dams (mHFD) exhibited a significant reduction in slow-twitch oxidative fibres (p < 0.001) and an increase in fast-twitch glycolytic fibres compared with controls. This was accompanied by impaired glucose tolerance (AUC increased by 12.87%, p < 0.01), insulin resistance and mitochondrial dysfunction (mtDNA copy number reduced by 31%, p < 0.01). RNA sequencing identified IDH2 as the most significantly downregulated gene (29.67% decrease, p < 0.001), with protein levels further reduced in male (30.15%, p < 0.01) and female (46.02%, p < 0.0001) offspring. IDH2 knockdown in C2C12 cells impaired mitochondrial biogenesis and led to higher oxidative stress (NADP+/NADPH ratio elevated by 32%, p < 0.01), while IDH2 overexpression restored mitochondrial integrity, enhanced slow-twitch fibre proportion (26.43 ± 0.6936% in mHFD-LV-IDH2, p < 0.01) and improved glucose metabolism (fasting glucose reduced by 14.7%, p < 0.01). ChIP-qPCR revealed increased H3K9me3 enrichment at the IDH2 promoter (2.54-fold in males, 2.55-fold in females, p < 0.0001), suggesting transgenerational epigenetic regulation.
conclusionsMaternal prepregnancy obesity induces a metabolic shift in offspring skeletal muscle by promoting a slow-to-fast fibre transition and impairing mitochondrial biogenesis. This effect is mediated by IDH2 suppression via H3K9me3 histone modification, contributing to systemic insulin resistance. Targeting IDH2 may represent a potential therapeutic strategy to mitigate metabolic dysfunction in offspring exposed to maternal prepregnancy obesity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.