Researchers have found a handy ‘on’ button that is lacking in obesity and could be used to boost physical activity.
Do you love and look forward to exercising or loathe and dread it?
Maybe you’re a bit of both, like the Back Page: only sheer force of will gets us up to the gym, but once we’re there, we grudgingly admit it can be kind of fun.
We’re not, alas, in the group of people at risk of overexercising or overtraining, and we’ve yet to experience the legendary endorphin rush we are always assured is associated with running.
But sometimes even we get into that rhythm during a spot of cardio or resistance where our muscles start clamouring for more, rather than less.
It’d be handy to be able to inspire that feeling before a workout, or to be able to give it to people who naturally lack it but could really benefit from the movement.
That’s the ultimate promise of a new study from Spain’s National Cancer Research Centre, which has identified protein activity in muscles that switches on the desire for more exercise.
That such a switch existed was already known, but not how it worked.
Skeletal muscle isn’t just dumb brawn but an endocrine organ, we learn from this Science Advances paper – one that secretes factors called myokines that communicate with distant organs. That’s what makes exercise so beneficial for metabolic status.
“Understanding the role of these myokines and their secretion in response to exercise holds great promise in preventing obesity and associated metabolic disorders,” they say.
In a combination of animal and human experiments, the team looked at the production and effects of the p38 protein, part of a crucial signalling pathway activated during exercise. It comes in four flavours – alpha, beta, delta and gamma – and has a range of positive or negative effects on glucose and insulin resistance, depending which flavour predominates.
In human subjects the team found both p38α and p38γ are activated in muscles during exercise.
Then they messed about with some mice genes.
Knockout mice lacking p38α expression had lower body weight (less fat) and better glucose metabolism and tolerance and were better at exercising than regular mice – they ran faster and were more coordinated on a balance beam (and there’s a test we would like to watch). They also had less liver fat.
Effectively, p38α deficiency protected these mice against obesity, metabolic disease and hepatic steatosis.
Mice lacking p38α produced more p38γ. Knocking out p38γ reversed the protection.
To test this protective effect they amped up p38γ and found the mice were a lot more active.
Enter interleukin-15.
The Back Page’s wires are easily tangled, and having an inflammatory cytokine show up as the hero in this context was for us a surprise. But IL-15 is apparently “a well-known myokine linked to locomotor activity control”. Every day’s a school day.
More IL-15 means “increased activation of the motor cortex and subsequent elevation in spontaneous locomotor activity”, the authors write.
Mice without p38α had more IL-15 than regular mice, but that went away when they knocked out p38γ as well.
Injecting mice with IL-15 increased their locomotor activity and decreased “depression-like behavior (less immobility) in the tail suspension test” (and there’s a test we would not like to watch).
After a lot of exercise, mice showed more of both p38γ and IL-15.
So did humans subjected to a similarly gruelling workout.
All this boils down to those two forms of the protein being activated by exercise but playing opposing roles, p38γ as the accelerator and p38α as the brake, with interleukin-15 as the fuel in this quickly deteriorating analogy.
The team then compared a cohort of humans with and without obesity and found the former had lower blood levels of IL-15.
Once the importance of IL-15 as a blood biomarker for the desire to exercise, says co-author Professor Guadalupe Sabio, “you would be able to study whether different types of exercises (weights, running, CrossFit …) stimulate this axis differently, and also if it has the same effect on obese and non-obese people. That can help coaches and personal trainers design their programs more efficiently.”
“We could even think about creating an IL-15 drug for people who are more in need of the positive effects of physical exercise, and less likely to do or maintain it. For example, people with obesity.”
Given the many benefits of exercise over just losing weight, Ozempic et al. may soon have a real competitor in town.
Send motivational playlists that don’t begin with Eye of the Tiger to penny@medicalrepublic.com.au.
