Science

Fitting into your jeans may be all about genes

According to the World Health Organization, more than one in 10 adults suffers from obesity and over 2.6 million people die from being obese and overweight every year. In many ways obesity has become a worldwide epidemic and finding a way to stop it has become crucial. Fortunately, a recent study suggests that a scientific method of minimizing obesity may lie somewhere in the near future.

Researchers at the Georgetown University Medical Center have revealed how the mutation of a single gene in mouse studies may explain obesity in humans.

The study, which was recently published on Nature Medicine’s website, observed that mice with a certain genetic mutation were unable to recognize the body’s message to discontinue eating. Since the brain’s response to hormones controlling appetite was being blocked, mice with the mutated gene experienced insatiable appetites that led to consequent weight gain.

While many factors have been linked to obesity, the “brain-derived neurotrophic factor” gene, also known as the “BDNF” gene, has been linked to severe obesity in animals and in several human studies. Although this mutation is rare in people, researchers believe this discovery “may open up novel strategies to help the brain control body weight” and may eventually lead to a drug that can stimulate the expression of BDNF in humans, according to the report in Nature.

HOW THE GENE WORKS

After eating, the body releases two hormones: leptin and insulin. These chemicals then signal a part of the brain that suppresses appetite. However, mice with the BDNF gene mutation cannot properly receive this message. When neurons are unable to pass leptin and insulin signals to the correct part of the brain, mutated mice experience an increased appetite that leads to weight gain. In the study, mice genetically altered to possess the BDNF mutation consumed up to 80% more food than those without the mutation.

Similarly in humans, insulin and leptin are released throughout the body after eating and signal the brain to discontinue consumption. When these signals do not reach the correct location in hypothalamus, the part of the brain responsible for satiety, a person’s appetite will remain ravenous and cause him or her to overeat.  Eventually, this overeating leads to severe obesity.

“If there is a problem with the BDNF gene, neurons can’t talk to each other, and the leptin and insulin signals are ineffective, and appetite is not modified,” said the study’s senior investigator, Baoji Xu, Ph.D., in a Science Daily report. Xu, who is also an associate professor of pharmacology and physiology at Georgetown, has studied the BDNF gene for many years. His research has demonstrated how hormones such as leptin and insulin stimulate the synthesis of BDNF in dendrites to move chemical signals between neurons through synapses. His data has also shown how the BDNF gene is responsible for a variety of other brain functions in mice, such as memory and learning.

SOLVING THE PROBLEM

Although the BDNF gene has been researched for several years, its link to weight control remained unclear until recently. However, now that scientists know how the BDNF mutation affects insulin and leptin chemical signals through brain neurons, their next predicament is finding ways to normalize it.

Xu and other researchers are investigating ways in which leptin and insulin signals might properly locate the part of the hypothalamus that suppresses appetite. According to researchers of the study, there have been several suggestions as to how to do this, but no single strategy has been completely supported.

According to Xu, one method would attempt to produce an additional long-form BDNF transcript using a virus-based gene therapy. However, while this form of gene therapy has been proven safe in other experiments, transporting anything across the brain blood barrier can be difficult.

Another strategy that has been suggested involves using a drug capable of stimulating the BDNF gene’s expression in the hypothalamus. While this is currently the most plausible method, using a drug also presents several issues. Eric Widmaier, a professor of biology at Boston University who has studied weight gain and obesity in mice for over 15 years, is one researcher who believes this method could be too risky.

“This protein is involved in lots of other things and lots of other functions,” Widmaier said. “If you’re going to manipulate it, you run the risk of influencing all of these other body processes.” This protein, Widmaier explains, is found in the kidneys, the prostate gland, and many other tissues other than the brain. It also plays an important role in the central nervous system and altering it could yield a variety of negative consequences.

“The only way you’re going to make this work is some sort of regulation of the gene itself,” he said. “How to do that is really problematic.”

SO WHEN WILL WE SEE A SOLUTION?

“We have opened the door to both new avenues in basic research and clinical therapies, which is very exciting,” Xu says. He and his team have much more research to conduct before employing a single method. Widmaier, however, seems less hopeful for a speedy solution.

“It’s certainly not in the near future,” Widmaier said. He believes finding a single solution anytime in our generation is highly unlikely. Despite this, however, Widmaier agrees that this study is a step ahead.

“Perhaps it’s just one more tool that someday they’ll be able manipulate and reduce somebody’s appetite and regulate their weight that way.”

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