The will to diet may not be enough; obesity reprogrammes the brain to just keep on eating
It’s no longer a question of will power. US scientists have shown how obesity disrupts the brain’s ability to regulate appetite, meaning that the fatter a person becomes, the more difficult it is to resist those extra portions.
It’s all down to leptin, a hormone released from fat cells or adipocytes, and the brain’s response to it.
Michael Cowley and colleagues at the Oregon Health and Science University compared obese mice to their slimmer counterparts. They showed that leptin was less effective at stimulating the release of appetite suppressing peptides in the brains of the fatter mice. Previous research indicates that obese humans are also resistant to this natural appetite suppressant.
The concept of leptin resistance has been around for some time and has proved to be a major stumbling block in the development of anti-obesity drugs. Cowley now thinks he has hit upon the chemical cause of this resistance and, in the process, a mechanism that might reverse it.
He and his team showed that a chemical signalling molecule called cytokine signalling- 3 (Socs-3), that interferes with leptin’s activity in neurons, might be the culprit.
’Socs3 appears to be [causing] the blockage here,’ Cowley told Chemistry World. ’If Socs3 inhibitors can prevent leptin resistance, and all the omens point that way, then they will be able to reinstate leptin sensitivity in obese organisms.’
Steve Bloom from Imperial College London, UK, is not so confident. His study of the appetite suppressing hormone pancreatic polypeptide spurred headlines earlier this year, when it was suggested that the hormone could be incorporated into an anti-obesity chewing gum.
’This is quite a contentious area,’ said Bloom. ’There are a number of theories and findings as to why fat people or animals become leptin resistant. It’s also not clear that this applies to humans.’
But Cowley says that his study provides strong evidence that Socs-3 is the crucial factor in leptin resistance. He explains that, while the rest of the brain’s appetite regulating circuitry is not disrupted in obese animals, there is a measured increase in the activity of Socs-3.
’This work shows a fundamental difference between the brains of lean and obese people,’ added Cowley. ’In some circles, there remains an impression that obesity is due to a failure to exert proper self control. This suggests that that just isn’t the case.’
et alCell Metab., 2007, DOI: 10.1016/j.cmet.2007.02.004