Maternal Obesity - Skeletal Muscle Multiomics Dataset

Description

Maternal obesity is a major developmental risk factor for lifelong metabolic dysfunction, yet the molecular mechanisms linking adverse maternal metabolic environments to fetal skeletal muscle programming remain poorly understood. Here, we performed an integrative multi-omics analysis combining embryonic skeletal muscle transcriptomics, DNA methylation profiling, independent lipid-overload validation and developmental datasets to identify conserved regulatory programmes underlying maternal obesity-induced developmental programming. Maternal obesity induced extensive transcriptional remodelling comprising 725 differentially expressed genes, with functional analyses unexpectedly identifying proteostasis-associated pathways, including endoplasmic reticulum stress, unfolded protein response, protein quality control and macroautophagy, as the dominant molecular signature, whereas developmental programmes associated with neuromuscular specification were suppressed. Transcriptome–methylome integration demonstrated widespread epigenetic support for these alterations and refined the molecular signature to a conserved subset of genes enriched for protein homeostasis, chromatin remodelling and nutrient-sensing pathways. Independent validation in linoleic acid-treated myotubes confirmed the reproducibility of this regulatory programme, whereas developmental validation in SIX1/4-regulated PAX7⁺ fetal myogenic progenitors demonstrated that the conserved signature was specifically enriched during early fetal myogenesis (E15.5), but not during later developmental stages (E18.5), indicating preferential association with early progenitor specification. Collectively, these findings identify a conserved developmental regulatory programme linking maternal obesity to proteostatic stress, epigenetic remodelling and nutrient-responsive signalling during embryonic skeletal muscle development, providing a systems-level framework through which adverse maternal metabolic environments may remodel early myogenic progenitor networks and contribute to lifelong susceptibility to skeletal muscle dysfunction and metabolic disease.

Institutions

• Universidade Federal do Rio Grande do Sul

  Rio Grande do Sul, Porto Alegre
• Universidade Federal do Paraná

  Paraná, Curitiba

Categories

Funders

• Conselho Nacional de Desenvolvimento Científico e Tecnológico

  Brasília

  Grant ID: 155029/2025-8

Licence