Drosophila in a vial after 24 h of centrifugation. Photo credit: Ruud Schilder.
No matter how often I get on the bathroom scales, they're never going to tip back to the weight that I was when I went to university. I've piled on a few pounds since then, but my legs never seemed to notice the difference. ‘It makes sense that animals should be able to “gauge” how heavy they are’, says Ruud Schilder from Pennsylvania State University, USA, as most creatures have to adjust the strength of their muscles over the course of their lifetime. ‘But we really do not understand well how such adjustments are achieved’, he continues. Having already shown that rats can modify their muscle by producing alternative versions of a muscle protein (troponin T, which can alter the amount of force produced by a muscle) in response to weight gain, Schilder decided to find out whether fruit flies (Drosophila melanogaster) also alter which forms of troponin T they produce when they put on weight.
Explaining his choice of animal, Schilder says, ‘Drosophila makes for an interesting organism to study this in, as there are many molecular tools we can use to study the mechanistic details of muscle adjustments’. However, Schilder and undergraduate student Megan Raynor had to come up with a creative solution to help the insects gain weight rapidly. ‘Fruit flies are fairly small, so attaching weights is not easy’, chuckles Schilder. Instead, he decided to tamper with gravity by spinning the insects at high speed to increase the force pulling on their bodies; ‘In other words, we tricked the fly leg muscles into thinking that they were supporting much heavier bodies’, he says. However, Schilder had to cobble together an impromptu centrifuge by cannibalizing the remains of a human treadmill and an office chair to increase the flies’ weight 12-fold from 0.49–0.77 mg to 5.88–9.24 mg. Spinning the flies for 24 h, Schilder and Raynor tested the strength of the flies’ legs and found that the insects were better climbers and jumpers. Their leg muscles were much stronger than those of flies that had not gained weight. And when Schilder checked how stressful the insects had found the experienced – by comparing the metabolic rate of the spun insects with that of insects that had remained static – he was surprised that the fruit flies were unaffected: ‘[they] seemed rather unimpressed by the whole affair’, he recalls.
However, when Schilder analysed which forms of troponin T (ranging from troponin T_A to troponin T_F) the flies were likely to be incorporating into their leg muscles, by looking at the different troponin T mRNA molecules (which are then converted into protein), he was impressed to see noticeable shifts in the mRNA distributions of the spun flies. One form (troponin T_A) dropped off dramatically in the legs of the bulkiest flies, while the legs of the daintiest insects produced almost as much of the troponin T_A mRNA as the unspun insects. ‘The effect of weight increase on troponin T transcription depended on the actual weight load experienced by Drosophila leg muscles’, says Schilder.
So, it seems that fruit flies have some sort of sensor that can detect when they are gaining weight that triggers leg muscle modifications, and the response is remarkably fast. Schilder also suspects that other animals may share the same mechanism, having previously discovered that rats also modify their muscles in response to weight gain. ‘We don't know yet what the sensors are, but our results support the existence of an evolutionarily conserved mechanism that translates body weight variation into appropriate skeletal muscle molecular and functional responses’, he says.