Obesity and its health consequences burden more and more people, especially in industrialised countries. Having too many fat deposits in the body drives up the risk of getting type 2 diabetes and cardiovascular diseases. Obesity is however not only reflected in body circumference, but can also be detected in the blood, because various fats from food circulate there. Increased blood lipid levels are a risk factor for heart attack and stroke.
Genetic control loop monitors fat in blood
A Swiss research group has developed an implantable genetic circuit which serves as an early warning system and as a therapy at the same time. On the one hand, it constantly monitors the levels of fats circulating in the blood. On the other hand, it acts via feedback and in response to excessively high blood lipids and produces a chemical messenger that gives the body a feeling of satiety. “The control loop is comprised of, among other things, a lipid sensor, which is also found in the human liver. Just as in nature this sensor monitors how much of our stored fat must be broken down when we take in too little food”, says study leader Prof. Dr. Martin Fussenegger of the ETH Zurich. If blood fat levels are too high, the sensor produces a satiation hormone that stops the intake of food. Through this mechanism blood fat levels fall back to a lower level and the sensor stops the production of the satiation hormone pramlintide. “Our loop is a so-called ‘closed loop ‘because it repeatedly and independently brings things to a normal level”, says Fussenegger.
Hooked up to the bloodstream
The highly complex loop was introduced by the scientists into human cells which they packaged in capsules made of algal gelatin. “Our capsules have a consistency of caviar, but are only about one-quarter the size”, the biotechnologist indicates. The pore size of the capsules was adjusted by the researchers so that mouse antibodies are not able to penetrate the capsule, in which case they would fight the human cells. The holes in the sensor cell capsules are however large enough to allow metabolites such as cellular foods and hormones to pass through. If the capsules are inserted into a mouse’s abdominal cavity fibroblasts accumulate there which connect the capsules to the bloodstream. The designer cells are thus optimally supplied with nutrients. The blood lipids in this way get to the cells as well, which in turn secrete the satiation hormone into the body through blood circulation.
The implant monitors the blood lipid levels and creates an appetite suppressant. (Graphic: M. Fussenegger / ETH Zurich; The Jackson Laboratory)
Obese mice satisfied sooner
To see whether their system works the biotechnologists studied obese mice that had been fattened up with fatty food. After they had implanted the capsules with the gene-control loop within them into the abdomen and the implants acted in response to the excessively elevated fat levels, the obese mice stopped eating. As a result, their body weight decreased measurably. The blood lipid levels also returned to normal, so that the loop stopped the formation of the satiation signal. “We did not set the mice on a diet, but left calorie-rich food available to the animals to take àt their own discretion“, emphasises Fussenegger. The animals ate less because the implant gave them a signal for satiety due to the blood lipid levels. Mice which received normal animal feed with five percent fat lost no weight and food intake was also not reduced, says the biotechnologist.
Sensor for different dietary fats
A major advantage of the new synthetic loop is that it is able not only to measure one kind of fat, but several saturated and unsaturated animal and vegetable fats in the body simultaneously. “It is important that this determination of blood lipid levels is based not only on the detection of a single fat, but can detect various fats from the diet, because otherwise it would not work reliably”, explains Prof. Fussenegger.
Soft against obesity
Obese people could be able to benefit from Fussenegger’s loop as well. The researcher sees the development as a possible alternative to surgical procedures such as liposuction or the gastric band. “Our implant would have the advantage that it can be used without such serious medical intervention”. Another advantage: it does not intervene in a difficult to regulate disease progression, but instead has a preventive effect and uses the natural satiation mechanism in human beings. “Obese people could still eat regularly, they would only be full sooner”, says Fussenegger. Before that happens, the biotechnologists’ control loop would still have to go through preclinical and clinical studies. “All of our components are already of human origin, and the satiation hormone has already been approved medically”, says Fussenegger. Once a manufacturing partner is found, things can start.
If these implants should come into use with people, Prof. Fussenegger expects that they would have to be replaced about every 3 to 4 months, because over time so many fibroblasts accumulate around the capsules as to consistently clog them: “A renewed implantation of the capsules would be relatively straightforward, as we could even place them in humans under the skin”. In the fight against excess pounds, frozen implants could be used as replacements by the family doctor about three to four times a year.