Drugs that mimic some of the effects of exercise can reduce signs of cardiovascular disease in overweight mice
We all know exercise has beneficial effects, but many people struggle to maintain adequate levels of exercise in today’s world and there are health consequences to this sedentary lifestyle – particularly when low activity is paired with obesity. Developing an exercise pill is therefore an attractive medical dream, and could stave off many of the diseases that are accelerated or increased by this damaging combination.
When scientists have studied exactly what mechanisms are activated or inhibited during exercise, they determined that one of the key changes is an activation of lipid metabolism genes; raising fat burning activity. After discovering the protein that normally blocks expression of these genes, a research team started creating a targeted drug to unleash these genes’ lipid burning activity during periods of rest too.
“Although it increases energy expenditure and fat burning, mice treated with the drug also ate a little bit more, meaning they remained weight stable”
The research builds on a previous study published in November 2015, which detailed over 1000 changes in skeletal muscle that occur in response to exercise. These changes provide a framework for creating various exercise mimicking drugs, and the latest effort uses drugs called HDAC inhibitors to switch on particular genes.
Under normal conditions class IIa HDACs (histone deacetylases) form a co-repressor complex which inhibits gene expression in particular areas of the genome. Mutants unable to form this complex appear to exhibit some exercise-like molecular behaviour, and a research team tested drugs that prevent this complex from being formed in an attempt to copy some of the molecular changes caused by exercise.
A partial success
Application of particular HDAC inhibitors increased whole body energy expenditure, increased mitochondrial biogenesis, and reduced fasting blood glucose and lipid concentration. All of these resemble some of the changes seen after exercise. The key word is ‘some’ however. While the treatment appeared to rejuvenate and improve markers linked to cardiovascular disease in mice, there are many other features that occur alongside exercise such as a rise in ‘feel good’ endorphins. In terms of human treatment exercise remains the best solution, but busy schedules and a lack of motivation mean that many people simply can’t maintain appropriate levels of activity. Furthermore, drugs that copy some of the effects could be beneficial in patients with impaired movement or illness.
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