Why knowing molecular and cellular plasticity of exercise and inactivity is important for human health

 

Frank W. Booth

Department of Biomedical Sciences; University of Missouri; Columbia Missouri 65211, USA

 

It is no longer debatable that epidemical data prove that lack of sufficient physical activity is associated with a higher prevalence of most chronic diseases. What is lacking now, as a follow-up, are molecular links between the initiation of physical inactivity and initial biochemical/molecular changes whose long-term consequences are increases in risk factors for chronic diseases. Identification of the molecular links from tobacco smoke and from asbestos exposure to lung cancer provided evidence to have successful legal decisions restricting their exposure. Changes in human behavior have to be driven by court decisions the fuel regulatory changes to encourage behavioral change. The contention here is that to change physical inactivity behavior, science must first show the molecular links from lack of physical activity to chronic diseases. Further, delineation of causal signals from inactivity to chronic disease will permit more a more optimal prescription of physical activity for primary and secondary prevention of chronic diseases. New models of physical inactivity have been developed that more closely approximate human physical inactivity. In rat model, denial of access to running wheels after a period of voluntary running by rats led to a drop in submaximal insulin-stimulated glucose uptake in the epitrochearis muscle and an increase in intra-abdominal fat. The decreased insulin sensitivity was related to decreased insulin binding, insulin receptor β subunit protein and tyrosine phosphorylation, Akt phosphorylation, and GLUT 4 protein after only 53 hours of ending the daily voluntary running (J Physiol 2005 562:829, 2005 and 565:911, 2005). In the human model, decreasing daily step number for 2 weeks, decreased whole body and peripheral insulin sensitivity and Akt phosphorylation during a hyperinsulinemic, euglycemic clamp; further the same subjects had a 7% gain in intra-abdominal fat (JAMA 299:1261, 2008). Future efforts need to identify the molecular triggers that initiate these early changes.

 

Key words: Exercise, health, physical inactivity, disease