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Sanford, J. A.

Publications and source records attributed to Sanford, J. A..

2 recordsLinked to original sources

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training and sex on its molecular landscape has not been fully established. Utilizing an integrative multi-omics approach with data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we identified profound sexual dimorphism in the dynamic response of rat scWAT to endurance exercise training. Despite similar cardiorespiratory improvements, only male rats reduced whole-body adiposity, scWAT adipocyte size, and total scWAT triglyceride abundance with training. Multi-omic analyses of adipose tissue integrated with phenotypic measures identified sex-specific training responses including enrichment of mTOR signaling in females, while males displayed enhanced mitochondrial ribosome biogenesis and oxidative metabolism. Overall, this study reinforces our understanding that sex impacts scWAT biology and provides a rich resource to interrogate responses of scWAT to endurance training.

molecular biology↗

Multiomic identification of key transcriptional regulatory programs during endurance exercise training

Transcription factors (TFs) play a key role in regulating gene expression. We conducted an integrated analysis of chromatin accessibility, DNA methylation, mRNA expression, protein abundance and phosphorylation across eight tissues in fifty rats of equally represented sexes following endurance exercise training (EET) to identify coordinated epigenomic and transcriptional changes and determine key TFs involved. We uncovered tissue-specific EET associated changes and TF motif enrichment across differentially expressed genes (DEGs), accessible regions (DARs), and methylated regions (DMRs). We discovered distinct routes of EET-induced regulation through either epigenomic alterations providing better access for TFs to affect target genes, or via changes in TF expression or activity enabling target gene responses. We identified TF motifs enriched among correlated epigenomic and transcriptomic alterations, DEGs correlated with exercise-related phenotypic and cell type composition changes, and EET-induced activity changes of TFs whose target genes are enriched for DEGs. This analysis elucidates the unique gene regulatory mechanisms mediating diverse transcriptional responses to EET across tissues.

genomics↗