Restricting calorie consumption has been proven to have many benefits and now a new study has revealed that body temperature plays a critical role in such diet-induced health benefits. Through their findings, the researchers are now hoping to create a medicinal compound that imitates the valuable effects of reduced body temperature.
The study has been conducted by teams from Scripps Research, led by Dr Bruno Conti and Dr Gary Siuzdak and published in the journal Science Signalling. Dr Conti has spent years studying how and why calorie restriction leads to better health, with the ultimate goal of translating his findings into medicines which could potentially mimic what occurs naturally when a person eats less.
In his previous research, he had consistently observed that when mammals consume less food, their body temperature drops accordingly. This is evolution’s way of helping mammals conserve energy until food is available again, explains Dr Conti. In humans and also other mammals, up to half of the food consumed daily is turned into energy simply to maintain core body temperature.
Dr Conti’s other research has shown that temperature reduction can cause an increased lifespan independently of calorie restriction and further that these effects involve activation of certain cellular processes most of which are yet to be identified.
Other studies also support Dr Conti’s findings and have shown that preventing a drop in body temperature can actually counteract positive effects of calorie restriction. Notably, in an experiment involving calorie-restricted mice, anti-cancer benefits were diminished when core body temperature remained the same.
The question Dr Conti addressed in the study was: "It's not easy to discern what's driving the beneficial changes of calorie restriction. Is it the reduced calories on their own, or the change in body temperature that typically happens when one consumes fewer calories? Or is it a combination of both?” Therefore, Dr Conti and his team designed an experiment that would allow them to independently evaluate the effects of reduced nutrients and those of body temperature.
They set out to compare a group of calorie-restricted mice housed at room temperature - about 22°C—to another group housed at 30°C. The warmer environment was set up to invoke ‘thermo-neutrality’, a state at which most animals cannot easily reduce their body temperature.
Using a new technology called activity metabolomics, Dr Siuzdak’s team then evaluated the mice by measuring their metabolites, or chemicals released by the animals’ metabolism. Using this process, the team was able to look for the molecules in the bloodstream and in the brain that are changed by the reduction of either nutrients or body temperature.
"The data we collected showed that temperature has an equal or greater effect than nutrients on metabolism during calorie restriction," Dr Conti said. Notably, the team has been successful in the first comprehensive profiling of the metabolites that are changed by temperature reduction.
Analysing the results from both groups of mice, the scientists were able to prioritise which metabolites were most responsible for triggering changes to core body temperature. In a separate experiment, they were also able to show that it is possible to administer certain metabolites as a drug to affect body temperature.
Dr Conti believes that further work to validate the changes induced by temperature during calorie restriction should provide novel targets for future medicines. He calls such medicines ‘temperature mimetics’ which he hopes will offer health-promoting effects without having to reduce body temperature.
