Brain tricked into thinking it is fasting to cope better with inflammation
Mice who have been tricked into thinking they are fasting manage inflammation more easily, according to neurobiologists at The University of Manchester and collaborators from the University of Naples ‘Federico II’, in Italy.
The study of mice and published in Current Biology is also the first to show that the well-established protective effects of fasting are at least in part mediated by the brain, rather than a lack of nutrients as generally thought.
Funded by the Medical Research Council, the scientific team show that tricking the brain into thinking it is fasting is sufficient to induce effects of real fasting in otherwise well-fed mice.
Scientist have long known that periodic fasting can help promote a range of health benefits including reducing the severity of chronic inflammation, immune system regeneration, alleviating side effects of chemotherapy and even promote longevity.
But the researchers now show it is possible to induce some of the beneficial effects of fasting in mice, without them actually fasting.
The team developed a way to switch on a group of about 5,000 specialist brain cells called AgRP neurons -a tiny figure compared to the 70 million or so nerve cells in the whole brain which are responsible for generating the feeling of hunger.
Using specialist imaging techniques they were able to visualise the effect of a systemic inflammation in the mice who’s specialist brain cells had been engineered to glow fluorescently.
Loss of appetite and negative energy balance are common features of infection and inflammation in all animals, but are thought to have protective roles by reducing nutrient availability to host and pathogen metabolism.
However, the team discovered that the AgRP neurons detect reduced level of nutrients and respond by sending back to the body signals which have anti-inflammatory effects. Artificially turning on these specialist brain cells was also sufficient to generate anti-inflammatory effects.
Senior of author Dr Giuseppe D’ Agostino from The University of Manchester said: “Though it can be seen as paradoxical, the beneficial effects of fasting during sickness are well known”.
“We have now discovered that the brain plays an important role in this mechanism.”
Dr Gabriella Aviello from the University of Naples added: “There is obviously a long way to go, but the hope is that if we can exploit this mechanism, there could be a way to develop fasting memetic therapies which generate the beneficial effects of fasting, in those medical conditions where calorie restrictions is less desirable or counterproductive.”
The paper Hypothalamic AgRP neurons exert top-down control on systemic TNF-α release during endotoxemia is available here