Molecule prevents fat combustion

February 14, 2012 By Peter Rüegg
Molecule prevents fat combustion
Severely obese persons (Body Mass Index more than 33) have increased concentrations of a signalling molecule in their fat that suppresses fat burning. Credit: istockphoto

ETH Zurich researchers have found a new role for a well-known signalling molecule, Hif1: the molecule suppresses the burning of fat, which may possibly promote obesity in humans.

Researchers in the group led by Willy Krek, Professor of at ETH Zurich, have bad news and good news for obese people. The scientists showed that a molecule, Hif1, is active in the of the abdominal fat in mice. It ensures that the fat does not melt away even when the diet is changed. High concentrations of this signalling molecule are also present in massively overweight people.

The good news: the process is reversible. When the researchers switched off the relevant molecule in mice, the suppressed metabolic route started working normally again, the mice burnt and the fat deposits melted away.

Hif1 helps when there is too little oxygen

Hif1 is always present when tissue becomes greatly enlarged very quickly and enters an oxygen-depleted state as a result. That is equally true for and for abdominal fat. Hif1 is a signalling pathway that is conserved in and is present in all and in all cell types.

Hif1 reprograms : the cells reduce the oxygen-consuming generation of energy via their power stations, the . Under the effect of Hif1 they obtain the energy to live through what is known as , which operates even without oxygen. Willi Krek says: “The Hif1 signalling pathway helps cells deal with oxygen starvation.” However, Hif1 also promotes the formation of new blood vessels that grow into new tissue to supply it with oxygen.

High concentration of Hif1 in white fat

The ETH Zurich researchers first observed the connection between Hif1 and abdominal fat based on a mouse model. The animals were exclusively fed a fat-rich diet and gained weight quickly. Ultimately the scientists found high concentrations of Hif1 in the adipose tissue of these mice. This indicates that the fatty abdomen of the mice has poor blood circulation and the white fat cells are suffering from oxygen deficiency.

However, the researchers were able to observe that Hif1 has a significant influence on the enlargement of fatty tissue when they switched off the molecule. As a result the fatty tissue in these mice stopped enlarging any further even when they continued to be fed a fat-rich diet. Their weight remained stable. These animals even lost weight when they were fed a normal diet. Krek sums it up: “From this we concluded that fat is burnt when Hif1 is absent. Even fat that had formed around the mouse hearts disappeared without being deposited in other organs.”

Fat burning suppressed

Finally the researchers also discovered the mechanism by which Hif1 prevents the combustion of fat. Hif1 reduces the production of an enzyme called Sirt2, which itself in turn regulates genes that play a central role in the burning of fat. So when Hif1 is switched off in the mice, the Sirt2 enzyme becomes highly active and boosts the burning of fat.

The ETH Zurich researchers also discovered this in tissue samples from obese and lean people. They found Hif1 in high concentrations and the enzyme Sirt2 in low concentrations in the fatty tissue of overweight people. On the other hand only traces of Hif1 were present in people of normal weight.

Possible therapy recognized

Possible treatments for obese people can also be inferred from the new findings. Because Hif1 does not switch the enzyme off completely, the burning of fat in overweight people could be stimulated by chemically activating Sirt2. This could cause fat to be broken down without blocking Hif1. The researchers plan further experiments on mice to clarify what effect activating Sirt2 has on the animals’ bodies. Developing a corresponding treatment for overweight people will therefore probably take some time.

Explore further: Staying slim could be in the genes

More information: Krishnan J et al.: Dietary obesity-associated Hif1α activation on adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system. Genes and Development 26. Online Publication 1st February 2012. DOI:10.1101/gad.180406.111

Related Stories

Staying slim could be in the genes

September 13, 2011
Some people carry more weight than others, even with similar diets, because of genes that encourage fat storage.

Gladstone scientists identify gene critical for cell responses to oxygen deprivation

November 3, 2011
Scientists at the Gladstone Institutes have identified a protein that kick–starts the response to low levels of oxygen, suggesting new lines of research relevant to a variety of potentially fatal disorders associated ...

Orexin: A hormone that fights fat with fat

October 4, 2011
The fat we typically think of as body fat is called white fat. But there's another type—known as brown fat—that does more than just store fat. It burns fat. Scientists used to think that brown fat disappeared after ...

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

slonko
not rated yet Feb 14, 2012
what was the bad news?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.