Scientists at the Cologne-based Max Planck Institute for Neurological Research and the Cluster of Excellence in Cellular Stress Responses in Ageing-associated Diseases (CECAD) at the University of Cologne have clarified an important step in this complex control circuit. They have succeeded in showing how the hormone insulin acts in the part of the brain known as the ventromedial hypothalamus. The consumption of high-fat food causes more insulin to be released by the pancreas.
The hypothalamus plays an important role in energy homeostasis: the regulation of the body's energy balance. Special neurons in this part of the brain, known as POMC cells, react to neurotransmitters and thus control eating behaviour and energy expenditure. The hormone insulin is an important messenger substance. Insulin causes the carbohydrate consumed in food to be transported to target cells (for example. muscles) and is then available to these cells as an energy source. When high-fat food is consumed, more insulin is produced in the pancreas, and its concentration in the brain also increases.
A research group led by Jens Brüning, Director of the Max Planck Institute for Neurological Research and scientific coordinator of the CECAD (Cellular Stress Responses in Aging-Associated Diseases) cluster of excellence at the University of Cologne has achieved an important step in the explanation of this complex regulatory process. As the scientists have shown, insulin in the SF-1 neurons – another group of neurons in the hypothalamus – triggers a signalling cascade.
Interestingly, however, these cells appear only to be regulated by insulin when high-fat food is consumed and in the case of overweight. The enzyme P13-kinase plays a central role in this cascade of messenger substances. In the course of the intermediary steps in the process, the enzyme activates ion channels and thereby prevents the transmission of nerve impulses. The researchers suspect that the SF-1 cells communicate in this way with the POMC cells.
"Therefore, in overweight people, insulin probably indirectly inhibits the POMC neurons, which are responsible for the feeling of satiety, via the intermediary station of the SF-1 neurons," supposes the scientist. "At the same time, there is a further increase in food consumption." The direct proof that the two types of neurons communicate with each other in this way still remains to be found, however.
In order to find out how insulin acts in the brain, the Cologne-based scientists compared mice that lacked an insulin receptor on the SF-1 neurons with mice whose insulin receptors were intact. With normal food consumption, the researchers discovered no difference between the two groups. This would indicate that insulin does not exercise a key influence on the activity of these cells in slim individuals. However, when the rodents were fed high-fat food, those with the defective insulin receptor remained slim, while their counterparts with functional receptors rapidly gained weight.
MEDICA.de; Quelle: Max-Planck-Gesellschaft