New appetite suppressants Zebrafish larvae help fight obesity

Zebrafish larvae show us new ways out of overweight?

Obesity is increasingly becoming a health problem. Changing the diet is difficult for many people affected. Again and again, the cravings and appetites get in the way. One possible approach is the use of appetite inhibitors. But these have only limited or too strong side effects. However, researchers have now been able to identify a whole range of new active ingredients for appetite regulation. The behavior of zebrafish larvae led the research team to these discoveries.

An international research team from the University of Zurich and Harvard University has discovered a number of novel appetite suppressants that could be used to treat obesity and obesity as well as anorexia. The focus of research is a newly developed method in which the behavior of zebrafish larvae is crucial. The study results have recently been published in the journal "Science Advances".

How zebrafish larvae discover new appetite suppressants

For the first time, the science team used a new research methodology that allows testing a huge amount of drugs to sort out inappropriate substances from the outset. It was dispensed with common biochemical methods. Instead, zebrafish larvae were used. The approximately four millimeters large animals are on the one hand very well biologically researched and on the other hand, they can grow very fast in huge quantities. The researchers were able to use the fish larvae in a short time to test more than 10,000 active ingredients that can influence the appetite.

The behavior of the animals provides information

The zebrafish larvae were fed with fluorescent paramecia. Based on the fluorescent dye, the researchers were able to determine how much the animals have 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 was analyzed for specific light and sound effects. In already known appetite suppressants such as nicotine, the researchers were able to prove that this system works.

Discovery by exclusion

From the 10,000 active ingredients tested, 500 substances crystallized, which either inhibited or stimulated the appetite of the fish larvae. However, half of these 500 substances caused behavioral changes in the animals. "Through the parallel analysis of several behaviors, we were able to sort out a large number of unspecific substances in the first step," reports the first author of the study Josua Jordi in a press release from the University of Zurich. This new approach worked right away, the team emphasizes.

Many appetite suppressants have serious side effects

As the researchers report, many medications that affect appetite have unwanted effects. As an example, the team calls the now taken off the market appetite suppressant rimonabant. This could lead to anxiety disorders and depression and trigger suicidal thoughts. "The complexity of brain structures raises the question of whether there are any active ingredients that trigger only a very specific behavior," says Jordi. The zebrafish larvae help to find such an active ingredient.

22 promising candidates

Of the 10,000 compounds tested on the zebrafish larvae, 22 were promising candidates. These were then tested in a further step on more complex organisms - in mice. Here were the same appetite-influencing effects that have been observed in the fish. However, the mice also showed that some of the substances affected the activity of central messengers in the brain. This undesirable effect has already been observed in earlier appetite modulators.

New ingredients for appetite modulation

However, according to the researchers, there were also some active substances that did not. "The most important finding, however, was that most of the substances did not interfere with any of these known systems," concludes Professor Florian Engert of Harvard University. This points to completely new mechanisms for appetite regulation. According to the researchers, this opens the door to a whole range of clinical applications and therapies for obesity and anorexia - with no harmful side effects. (Vb)