Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery

Blackwell, James E.M.; Gharahdaghi, Nima; Deane, Colleen S.; Brook, Matthew S.; Williams, John P.; Lund, Jonathan N.; Atherton, Philip J.; Smith, Ken; Wilkinson, Daniel J.; Phillips, Bethan E.

Abstract

BACKGROUND: Surgery for urological cancers is associated with high complication rates and survivors commonly experience fatigue, reduced physical ability and quality of life. High-intensity interval training (HIIT) as surgical prehabilitation has been proven effective for improving the cardiorespiratory fitness (CRF) of urological cancer patients, however the mechanistic basis of this favourable adaptation is undefined. Thus, we aimed to assess the mechanisms of physiological responses to HIIT as surgical prehabilitation for urological cancer.
METHODS: Nineteen male patients scheduled for major urological surgery were randomised to complete 4-weeks HIIT prehabilitation (71.6 ± 0.75 years, BMI: 27.7 ± 0.9 kg·m 2) or a no-intervention control (71.8 ± 1.1 years, BMI: 26.9 ± 1.3 kg·m 2). Before and after the intervention period, patients underwent m. vastus lateralis biopsies to quantify the impact of HIIT on mitochondrial oxidative phosphorylation (OXPHOS) capacity, cumulative myofibrillar muscle protein synthesis (MPS) and anabolic, catabolic and insulin-related signalling.
RESULTS: OXPHOS capacity increased with HIIT, with increased expression of electron transport chain protein complexes (C)-II (p = 0.010) and III (p = 0.045); and a significant correlation between changes in C-I (r = 0.80, p = 0.003), C-IV (r = 0.75, p = 0.008) and C-V (r = 0.61, p = 0.046) and changes in CRF. Neither MPS (1.81 ± 0.12 to 2.04 ± 0.14%·day −1 , p = 0.39) nor anabolic or catabolic proteins were upregulated by HIIT (p > 0.05). There was, however, an increase in phosphorylation of AS160 Thr642 (p = 0.046) post-HIIT.
CONCLUSIONS: A HIIT surgical prehabilitation regime, which improved the CRF of urological cancer patients, enhanced capacity for skeletal muscle OXPHOS; offering potential mechanistic explanation for this favourable adaptation. HIIT did not stimulate MPS, synonymous with the observed lack of hypertrophy. Larger trials pairing patient-centred and clinical endpoints with mechanistic investigations are required to determine the broader impacts of HIIT prehabilitation in this cohort, and to inform on future optimisation (i.e., to increase muscle mass).

• Journal Article Type: Article
• Acceptance Date: Nov 24, 2023
• Online Publication Date: Dec 18, 2023
• Publication Date: Dec 18, 2023
• Deposit Date: Dec 18, 2023
• Publicly Available Date: Dec 18, 2023
• Journal: Prostate Cancer and Prostatic Diseases
• Print ISSN: 1365-7852
• Electronic ISSN: 1476-5608
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1038/s41391-023-00774-z
• Keywords: Cancer Research, Urology, Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/28705535
• Additional Information: This is the peer reviewed version of the following article: Blackwell, J. E., Gharahdaghi, N., Deane, C. S., Brook, M. S., Williams, J. P., Lund, J. N., …Phillips, B. E. (2023). Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery. Prostate Cancer and Prostatic Diseases, which has been published in final form at https://doi.org/10.1038/s41391-023-00774-z