Key mechanism of insulin in brain leading to obesity decoded

Researchers at the Max Planck Institute for Neurological Research in Cologne have decoded a key mechanism through which insulin in the brain controls the body's energy balance.

They have shown how insulin action in the part of the brain known as the ventromedial hypothalamus can lead to obesity.

The consumption of high-fat food causes more insulin to be released by the pancreas. This triggers a signalling cascade in special nerve cells in the brain, the SF-1 neurons, in which the enzyme P13-kinase plays an important role. Over the course of several intermediary steps, the insulin inhibits the transmission of nerve impulses in such a way that the feeling of satiety is suppressed and energy expenditure reduced. This promotes overweight and obesity.

However, the precise molecular mechanisms that lie behind the control exercised by insulin remain largely unclear.

In order to find out how insulin acts in the brain, a research group led by Jens Bruning 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. The weight gain was due to both an increase in appetite and reduced calorie expenditure.

This effect of insulin could constitute a evolutionary adaptation by the body to an irregular food supply and extended periods of hunger, if an excess supply of high-fat food is temporarily available, the body can lay down energy reserves particularly effectively through the action of insulin.

The researchers, however, cautioned that it was not currently possible to say whether their findings would eventually help to facilitate targeted intervention in the body's energy balance.