Browsing by Author "Houmard, Joseph A."

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    Sex-Specific Skeletal Muscle Gene Expression Responses to Exercise Reveal Novel Direct Mediators of Insulin Sensitivity Change
    (Oxford University Press, 2025-03-28) Ma, Sisi; Hubal, Monica J.; Morris, Matthew C.; Ross, Leanna M.; Huffman, Kim M.; Vann, Christopher G.; Moore, Nadia; Hauser, Elizabeth R.; Bareja, Akshay; Jiang, Rong; Kummerfeld, Eric; Barberio, Matthew D .; Houmard, Joseph A.; Bennett, William C.; Johnson, Johanna L.; Timmons, James A.; Broderick, Gordon; Kraus, Virginia B.; Aliferis, Constantin F.; Kraus, William E.; Exercise & Kinesiology, School of Health and Human Sciences
    Understanding how exercise improves whole-body insulin sensitivity (Si) involves complex molecular signaling. This study examines skeletal muscle gene expression changes related to Si, considering sex differences, exercise amount, and intensity to identify pharmacologic targets mimicking exercise benefits. Fifty-three participants from STRRIDE (Studies of Targeted Risk Reduction Interventions through Defined Exercise) I and II completed eight months of aerobic training. Gene expression was assessed via Affymetrix and Illumina technologies, and Si was measured using intravenous glucose tolerance tests. A novel discovery protocol integrating literature-derived and data-driven modeling identified causal pathways and direct transcriptional targets. In women, exercise amount primarily influenced transcription factor targets, which were generally inhibitory, while in men, exercise intensity drove activating targets. Common transcription factors included ATF1, CEBPA, BACH2, and STAT1. Si-related transcriptional targets included TACR3 and TMC7 for intensity-driven effects, and GRIN3B and EIF3B for amount-driven effects. Two key pathways mediating Si improvements were identified: estrogen signaling and protein kinase C (PKC) signaling, both converging on the epidermal growth factor receptor (EGFR) and other relevant targets. The molecular pathways underlying Si improvements varied by sex and exercise parameters, highlighting potential skeletal muscle-specific drug targets such as EGFR to replicate the metabolic benefits of exercise.
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    Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery
    (Frontiers Media, 2021-10-06) Barberio, Matthew D.; Dohm, G. Lynis; Pories, Walter J.; Gadaleta, Natalie A.; Houmard, Joseph A.; Nadler, Evan P.; Hubal, Monica J.; Exercise & Kinesiology, School of Health and Human Sciences
    Introduction: Roux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes mellitus (T2DM) that can result in remission of clinical symptoms, yet mechanisms for improved skeletal muscle health are poorly understood. We sought to define the impact of existing T2DM on RYGB-induced muscle transcriptome changes. Methods: Vastus lateralis biopsy transcriptomes were generated pre- and 1-year post-RYGB in black adult females with (T2D; n = 5, age = 51 ± 6 years, BMI = 53.0 ± 5.8 kg/m2) and without (CON; n = 7, 43 ± 6 years, 51.0 ± 9.2 kg/m2) T2DM. Insulin, glucose, and HOMA-IR were measured in blood at the same time points. ANCOVA detected differentially expressed genes (p < 0.01, fold change < |1.2|), which were used to identify enriched biological pathways. Results: Pre-RYGB, 95 probes were downregulated with T2D including subunits of mitochondrial complex I. Post-RYGB, the T2D group had normalized gene expression when compared to their non-diabetic counterparts with only three probes remaining significantly different. In the T2D, we identified 52 probes upregulated from pre- to post-RYGB, including NDFUB7 and NDFUA1. Conclusion: Black females with T2DM show extensive downregulation of genes across aerobic metabolism pathways prior to RYGB, which resolves 1 year post-RYGB and is related to improvements in clinical markers. These data support efficacy of RYGB for improving skeletal muscle health, especially in patients with T2DM.