Study: Mice lose weight from simulation of cold, nicotine

Oct. 25 (UPI) -- By stimulating the effects of cold and nicotine, mice lost significant weight, according to a study.

Researchers stimulated the so-called cold and nicotinic receptors, causing the mice to burn more energy, suppress the appetite and produce weight loss. Besides increasing their metabolism, glucose intolerance, which is tied to type 2 diabetes, disappeared.

The findings were published this week in the journal Nature Communications.

The researchers conducted the experiments to mimic the belief that the effects of winter swimming and smoking lead to weight loss.

"If you want to change people's body weight, it is not enough to target the energy turnover alone," Dr. Christoffer Clemmensen, an associate professor in health and medical Sciences at the University of Copenhagen in Denmark, said in a press release. "To really create a negative energy balance, you also have to make people eat less."

They first attempted to activate the so-called cold receptors found in connection with winter swimming. The body's so-called brown fat burns energy.

"We tried to find the molecular mechanisms for the way in which cold increases the burning of energy in order to duplicate them in a medical product," Clemmensen said. "We found a cold receptor -- TRPM8 -- and identified the substance icilin which can activate it."

They found the cold receptor is not found in brown fat, but rather it's on the surface of the skin that 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," Clemmensen said. "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."

They looked for something to combine with icilin treatment. They focused on the receptor that is activated by nicotime. Testing various pharmacological substances, they found dimethylphenylpiperazinium could activate nicotinic receptors.

"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 said. "We therefore combined icilin and DMPP and achieved what you might call a synergy effect on body weight."

Mice experienced a weight loss of about 12 percent over 20 days.

"This means that two plus two add up to more than four," Clemmensen said. "On their own, they do not produce any particular weight loss, but when we give them together, we see a big weight loss."