Oleic Acid Levels in HSA^LR Mouse Model of Myotonic Dystrophy Type 1

Myotonic dystrophy type 1 (DM1) is characterized by altered RNA processing, muscle wasting and metabolic dysregulation. In a previous in vitro study, we found reduced endogenous oleic acid (OA; 18:1n-9) in myogenic cells from DM1 patients, and short-term OA supplementation rescued key disease readouts. Here, we asked whether lipid pathways are perturbed in a DM1 in vivo background. We employed the widely used HSA^LR mouse model, which expresses human skeletal alpha-actin transcripts harbouring expanded CTG repeats and recapitulates key DM1 phenotypes. RNA-seq-derived functional enrichment across three independent HSA^LR datasets revealed a consistent enrichment of downregulated GO terms related to fatty-acid metabolism, suggesting impaired lipid handling. Guided by transcriptomic evidence of fatty-acid pathway downregulation, we quantified endogenous OA in HSA^LR mice versus FVB controls by LC-MS across sex, age (postnatal day 21 and 4 months) and tissue (quadriceps, gastrocnemius, and plasma), reporting values per tissue weight and per total protein. OA showed selective, context-dependent reductions in skeletal muscle, varying with tissue, sex, age and normalization, with the clearest deficits in males and in the gastrocnemius, while no generalized deficit was observed. Plasma OA was transiently higher at P21 in both sexes, consistent with the oleate-rich weaning mice diet. Together, the RNA-seq enrichment signal for fatty-acid pathways and the context-dependent OA changes point to network-level control (substrate supply, partitioning/transport, cofactors or downstream utilization), positioning OA as a potential measurable candidate marker of DM1-like muscle pathology in HSA^LR mice.