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The brain may control cholesterol

Cholesterol levels are controlled by a “hormone in the brain” the Daily Mail has reported.

It says the finding offers hope of new treatments to reduce levels of “the dangerous fat”.

The Mail’s story is based on animal research that appears to indicate that blood cholesterol levels are regulated remotely by the central nervous system. The researchers found that increasing levels of a hormone called ghrelin, which is thought to regulate energy intake, caused mice to develop higher levels of cholesterol. The finding that cholesterol can be regulated by the brain could be the basis for new drug treatments, they suggest.

The findings are interesting, but it is important to stress that there are large differences in the way cholesterol affects mice and humans. This is early research that points the way to further research into ghrelin, although more human studies are needed to draw firm conclusions about the brain regulating human blood cholesterol levels. It’s also important to note that, in humans, cholesterol levels can be controlled by diet, exercise and, where necessary, drug treatment.

Where did the story come from?

The study was carried out by researchers from various centres including the University of Cincinnati College of Medicine in Ohio, Indiana University at Bloomington and the Institute of Animal Science in Schwerzenbach, Switzerland. It was funded by grants from the US National Institutes of Health and published in the peer-reviewed medical journal Nature Neuroscience.

The study’s main findings were reported accurately by the BBC, which pointed out that the findings need to be replicated in humans. Its story also included advice on controlling cholesterol from the British Heart Foundation.

The Daily Mail also pointed out that more work is needed, but incorrectly identified high-density lipoprotein (HDL) as the type of  cholesterol that can lead to hardening of the arteries and called low-density lipoprotein (LDL) ‘good’ cholesterol. This is the wrong way around. The Mail’s headline also claimed that the findings gave “hope for new drugs” and the story went on to say that current drugs for cholesterol, called statins, have many side effects. It did not point out that any new drug for cholesterol will need to go through several stages to test for efficacy and safety before being made available or that any new drug also has a risk of side effects.

What kind of research was this?

Cholesterol is a fat-like substance that circulates in the blood. HDL, or ‘good’, cholesterol is beneficial, while high levels of ‘bad’ LDL cholesterol carry a risk of cardiovascular disorders, such as heart disease. Research so far has found that, in humans, blood levels of cholesterol are regulated by dietary intake and synthesis by the liver.

The researchers point out that lipid disorders such as high cholesterol, together with obesity, high blood pressure and impaired glucose metabolism, all raise the risk of cardiovascular disorders and obesity can raise the risk of diabetes.

Efforts to find drugs for these disorders have found that the hormone ghrelin, produced by the gut, and believed to inform the brain about energy availability, is already implicated in some of these disorders. 

Ghrelin is believed to have an effect on a chemical called melanocortin produced by the part of the brain called the hypothalamus. Melanocortin in turn regulates factors such as fatty tissue, glucose metabolism and blood pressure. The researchers wanted to test their hypothesis that a neural circuit in the brain, the “gut-brain axis” involving both ghrelin and melanocortin, controls levels of blood cholesterol.

This was an animal study, conducted in the laboratory, using mice and rats to test the researchers’ hypothesis that cholesterol levels are regulated by the central nervous system. However, because cholesterol and the hormones were not measured in humans, its results may have only limited relevance.

What did the research involve?

The researchers conducted several experiments on a group of mice and rats. All the procedures used were in line with US guidelines for the care and use of laboratory animals and approved by the relevant institutions.

The mice in one group were given daily injections of ghrelin under the skin for one week, while another group of mice acted as a control. In a separate experiment, the researchers attempted to find out if the effects of ghrelin were limited by a chemical called melanocortin receptor antagonist (MC4R). To do this they deleted or chemically blocked the production of MC4R.

The animals were humanely killed and tissues frozen and their cholesterol levels analysed using standard chemical methods.

What were the basic results?

The researchers found that giving the mice the hormone ghrelin for one week not only caused the expected increase in body fat, but also significantly increased total blood cholesterol levels, compared with a control group. Levels of blood glucose and fats called triglycerides remained unchanged.

They also found that when they genetically deleted or blocked the melanocortin receptor (MC4R) in the central nervous system of the mice, it produced increased levels of ‘good’ HDL cholesterol. They thought part of the reason for this might be that the neural circuit reduces the uptake of cholesterol by the liver.

How did the researchers interpret the results?

The researchers conclude that the neural circuit in the brain involving the hormone ghrelin directly controls cholesterol metabolism by the liver. They say their study shows for the first time that cholesterol is under remote but direct control by specific neuroendocrine circuits in the central nervous system. They say this may lead to new drug treatments that can modulate melanocortin and, therefore, treat high cholesterol as well as other disorders related to the metabolism.

Conclusion

This is an interesting laboratory study that showed that, in mice, levels of blood cholesterol can be increased by raising the levels of the hormone ghrelin and blocking the melanocortin receptor. This suggests that the central nervous system has a role in the production of cholesterol.

However, more work is needed before these findings could be directly applied to humans. In addition, any new drug treatments based on this hypothesis would have to undergo several stages of trials for safety and efficacy before they could be made available to humans.

It’s important to note that there is good evidence that human cholesterol levels can be controlled by eating a diet low in saturated fats, exercising regularly and, where necessary, with drug treatment.

Links to the headlines

Cholesterol is controlled by a hormone in the brain, scientists find, giving hope for new drugs. Daily Mail, June 7 2010

Brain regulates cholesterol in blood, study suggests. BBC News, June 7 2010

Links to the science

Perez-Tilve D, Hofmann SM, Basford J et al.Melanocortin signaling in the CNS directly regulates circulating cholesterol. Nature Neuroscience [Published online] June 6 2010

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