Cross-talk between physiological systems: A new paradigm for exercise science? Professor Phil Jakeman

Much is known of the time course and nature of adaptation of specific human systems (e.g. cardiovascular, pulmonary, musculoskeletal) to acute (single bout) and chronic (training) exercise. Recent understanding of the interactive nature of periodicity, modality and sequencing of training has advanced coaching science. The cross-talk between physiological systems (e.g. the influence of myokine release form exercising muscle on hepatic or adipose tissue function) has now entered this complex mix and presents a new paradigm for exercise science.

The Human Science Research Group (HSRG @ UL) is exploring how this cross-talk is achieved. We believe the conduit for communication between physiological systems is the estimated 170km network of vessels that perfuse all tissues with to varying amounts dependent on requirement. This tightly regulated system can, for example, direct 50% of the 5 L/min resting cardiac output to only 15% of total body organ mass (liver, spleen, kidney, heart brain) whilst restricting the flow to skeletal muscle (approx. 60% of the organ mass) to 10%. Yet, during exercise, when cardiac output is elevated (e.g. to 20 L/min) >80% of the elevated flow is directed to skeletal muscle (approx. 30 fold increase).

Blood brought via the vasculature to the tissue/organ can exchange nutrient and organ derived molecules with the interstitial fluid of the various organs/cells influencing the regulatory microenvironment of the tissue and, similarly, blood draining from the organ tissue is the conduit for regulatory molecules from the organ/tissue to enter the central circulation. Given plasma volume ~3 L (~7% of total body water, TBW) and an interstitial volume of 13 L (~30% of TBW) organs that command a large flow, such as the liver at rest and skeletal muscle during exercise, are potent contributors to change in regulatory molecules in the tissue/organ microenvironment.

To date we have shown that it is possible to measure the change in the tissue microenvironment in response to feeding and exercise in human subjects in vivo[1,2] and, in real time, the time-course and magnitude of response (i.e. growth) of muscle cells incubated in ‘conditioned’ media replicating these changes in vitro[3] . It has also been possible to determine some of the key regulators present in the tissue microenvironment (growth factors, hormones, cytokine etc.) and the regulation of key cellular processes e.g. muscle protein synthesis and breakdown. This work has laid the foundation for new discovery of how, for example, the turnover of protein in skeletal muscle, collagen in bone and ligaments, fat in the adipose, is regulated by nutrient intake, exercise and, importantly, nutrient x exercise interaction. So watch this space!

Finally, though the majority of our investigation focus on healthy subjects, it is important to recognize that many of the principal components of this emerging paradigm are relevant to disease. Though not the panacea, examples of the beneficial effects of exercise as a preventative behaviour, adjunct therapy and potential ‘cure’ abound. For those who are interested in exploring this further the recent opinion in Nature Reviews[4] provides a stimulating introduction to the putative role of exercise in the regulation of the tumour microenvironment, i.e. in cancer-related disease.

  1. McCormack WG, Cooke JP, O’Connor WT, Jakeman PM. Dynamic measures of skeletal muscle dialysate and plasma amino acid concentration in response to exercise and nutrient ingestion in healthy adult males. Amino Acids. 2017, 49(1):151-159.
  2. Carson BP, McCormack WG, Conway C, Cooke J, Saunders J, O’Connor WT, Jakeman PM. An in vivo microdialysis characterization of the transient changes in the interstitial dialysate concentration of metabolites and cytokines in human skeletal muscle in response to insertion of a microdialysis probe. Cytokine. 2015, 71(2):327-33.
  3. Murphy SM, Kiely M, Jakeman PM, Kiely PA, Carson BP. Optimisation of an in vitro bioassay to monitor growth and formation of myotubes in real time. Biosci Rep. 2016, 36(3).
  4. Koelwyn GJ, Quail DF, Zhang X, White RM, Jones LW. Exercise-dependent regulation of the tumour microenvironment. Nat Rev Cancer. 2017 Sep 25;17(10):620-632

 

Phil J roundPhil Jakeman is a Professor of Exercise Science at the department of Physical Education and Sport Sciences in UL. He directs the Human Science Research Group within the 4i Centre for Intervention in Infection, Inflammation and Immunity at UL.  His research interests include Human Exercise Science, Biochemistry of Exercise, Growth Factors, Bone Turnover, Muscle Adaption, Nutrition and Metabolism.  Professor Jakeman can be contacted via email phil.jakeman@ul.ie or you can view his digital profile on Orchid   and view his publications on Researcher ID

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