Fat-Burning Discovery To Combat Obesity, National University of Singapore (NUS) Study

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Fat-Burning Discovery To Combat Obesity

Excessive weight, the cause of multiple health issues such as high blood pressure, heart diseases and diabetes, is becoming a worldwide epidemic. A recent breakthrough by a group of NUS scientists explaining why the fat keeps piling up will provide crucial knowledge in the battle against the flab.

Leading the study was Professor Carlos Ibanez from the NUS Department of Physiology and Life Sciences Institute. He said that although the mechanisms of fat deposits are already established, the reason for fat or adipose tissue’s resistance to being broken down remains a mystery. The team was the first to confirm the link between diet and fat storage, and its regulation by a receptor called ALK7. The work published in online journal eLife in August also provides proof-of-principle for the feasibility of a therapeutic approach to address obesity.

According to the World Health Organization, an estimated 1.4 billion people above 20 years were overweight in 2008 across the globe. Of these, about half a billion were obese. In Singapore, 10.8 per cent of adults aged between 18 and 69 years were obese in 2010, almost double that in 1992.

Genetics, lifestyle and environmental factors contribute to obesity, pointed out Prof Ibanez. Modern humans have progressed from the caveman era—when scarcity of food and starvation were the rule—to the present day where food supply is readily available. However, the genes involved have not evolved in tandem and still behave in the same manner, converting the extra calories into fats and chalking up the reserves. Furthermore, humans do less physical activities now while ingesting more calories than required. The result—a growing population of overweight people.

The NUS investigators conducted experiments on engineered mice with ALK7 shut down. When fed a high-fat diet, the animals put on only half of the weight gained by normal mice. This demonstrates that suppressing the receptor leads to higher burning of the fat cells.

“The discovery is the mechanistic link between the diet and the resistance of the adipose tissue to burn the fat. ALK7 is one of the first links found—a high-calorie diet enhances the signalling of this receptor,” Prof Ibanez said.

In another experiment, the team grew mice with an ALK7 mutation which makes them sensitive to a special chemical. When put on a high-fat diet, these chemical-injected animals increased by half the weight of their normal peers which were not injected. Tests on human adipose cells also demonstrated that the receptor works similarly in human cells.

This interesting observation shows that inhibition of the receptor can prevent obesity in adult animals. It suggests that blocking the human ALK7 could be a new strategy to fight obesity in people, as the receptor could be blocked whenever required by administering a chemical or drug. The development of specific inhibitors for the human variant of ALK7, however, remains something to be accomplished. Industrial laboratories are currently racing to achieve this.

The NUS team, who collaborated with the Karolinska Institutet in Sweden and the University of California, San Francisco, US, on the study, will be looking into whether obesity in mice can be reverted after administration of special chemicals.

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