Do zebrafish larvae show us new ways of being overweight?
Obesity is becoming a health problem. However, many affected people find it difficult to change their diet. Again and again they get in the way of cravings and appetites. One possible approach is to use appetite inhibitors. However, these only work to a limited extent or show excessive side effects. However, researchers have now succeeded in identifying a whole range of new active ingredients for appetite control. The behavior of zebra fish larvae led the research team to these discoveries.
An international team of researchers from the University of Zurich and the American Harvard University have discovered a number of new appetite suppressants that could be used to treat obesity and obesity as well as to treat anorexia (anorexia). Research focuses on a newly developed method in which the behavior of zebra fish larvae is crucial. The study results were recently published in the scientific journal "Science Advances".
How zebra fish larvae discover new appetite suppressants
For the first time, the scientific team used a new research method that allows a huge amount of active substances to be tested in order to sort out unsuitable substances from the outset. Common biochemical methods were not used. Instead, zebra fish larvae were used. The animals, which are around four millimeters in size, are very well researched biologically on the one hand and on the other hand they can be grown very quickly in huge quantities. With the help of the fish larvae, the researchers were able to quickly test more than 10,000 active substances that could influence appetite.
The behavior of the animals provides information
The zebra fish larvae were fed with fluorescent slipper animals. Using the fluorescent dye, the researchers were able to determine how much the animals had eaten. In this way, the research team was also able to see to what extent the eating behavior changed when certain active ingredients were used. In addition, the behavior of the larvae in relation to certain light and sound effects was analyzed. With well-known appetite suppressants like nicotine, the researchers were able to prove that this system works.
Discovery through exclusion
From the 10,000 active ingredients tested, 500 substances crystallized that either inhibited or stimulated the appetite of the fish larvae. However, half of these 500 substances caused behavior changes in the animals. "By analyzing several behaviors in parallel, we were able to sort out a large number of non-specific substances in the first step," reports the first author of the Josua Jordi study in a press release from the University of Zurich. The team emphasized that this new approach worked right away.
Many appetite suppressants have serious side effects
As the researchers report, many drugs that affect appetite have undesirable effects. As an example, the team names the appetite suppressant Rimonabant, which has since been withdrawn from the market. This could lead to anxiety disorders and depression and trigger suicidal thoughts. "Due to the complexity of the brain structures, the question arises whether there are any active ingredients that only trigger a very specific behavior," said Jordi. The zebra fish larvae help to find such an active ingredient.
22 promising candidates
Of the 10,000 active substances that were tested on the zebra fish larvae, 22 promising candidates remained. In a further step, these were then tested on more complex organisms - on mice. Here the same appetite-influencing effects were seen that were already observed in the fish. However, the mice also showed that some of the substances influenced the activity of central messenger substances in the brain. This undesirable effect has been observed with previous appetite modulators.
New active ingredients for appetite modulation
In addition, according to the researchers, there were also some active ingredients that did not. "However, the most important finding was that most of the substances did not interfere with any of these known systems," summarizes Professor Florian Engert from Harvard University. This points to completely new mechanisms for controlling appetite. According to the researchers, this opens a door for a whole range of clinical applications and therapies for obesity and anorexia - without harmful side effects. (vb)