Danish scientists may have stumbled upon a completely new pharmacological strategy to induce fat loss. The Danes discovered that an approach that simultaneously stimulates two types of receptors leads to an unprecedented rapid fat loss. In mice the combination of icilin and DMPP seems to be a real fat shredder. TRPM8 The receptor TRPM8 is located in the outer layers of the skin, where it registers cold. If TRMP8 is activated, fat burning will increase due to, among other things, an increase of fat oxidation in brown adipose tissues. A substance like menthol stimulates the TRMP8 receptor. However, the researchers discovered a synthetic compound that stimulates TRMP8 and it's called icilin. And so they injected fattened mice every day with different doses of icilin, and saw that the animals lost fat because their energy expenditure increased. "However, the cold receptor [TRMP8] is not found on brown fat", says first author Christoffer Clemmensen, affiliated with the University of Copenhagen. [sciencedaily.com October 24, 2018] "It seems that the cold receptor on the surface of the skin sends a signal to the brain that subsequently activates the brown fat via nerve connectors." "The mice became slimmer when they were given icilin because it increased their energy turnover. This confirmed our idea. However, the effect we saw was not sufficiently strong to have any actual effect for patients, even if we could optimize the medical product. If you want to change people's body weight, it is not enough to target the energy turnover alone. To really create a negative energy balance, you also have to make people eat less." Nicotinic acetylcholine receptor (nAChR) subtype alpha3beta4 Smokers eat less than people who do not smoke, and that is partly because the nicotine in their cigarettes activates the nicotinic acetylcholine receptor (nAChR) subtype alpha3beta4. The Danes discovered that the synthetic substance dimethylphenylpiperazinium [DMPP] works in the same way. And so they injected that substance into fattened mice. The animals ate less and lost weight. "DMPP not only suppresses the appetite, it also has a huge positive effect on glucose metabolism as opposed to nicotine, which has a poor effect on fat in the liver and insulin sensitivity", Clemmensen says. "We therefore combined icilin and DMPP and achieved what you might call a synergy effect on body weight." "This means that two plus two add up to more than four. On their own, they do not produce any particular weight loss, but when we give them together, we see a big weight loss." Conclusion Whether the resources used also work in people, and whether they are safe, the researchers do not know. They see their animal study as a proof of principle, no more, but no less.