How might a hormone aid weight loss in obesity?
Research in humans and monkeys suggests that lipocalin-2 (LCN2), which is a hormone that plays a role in feeling full after consuming a meal, might be able to help people lose weight.
Previous studies have suggested that when mice receive LCN2 over a period of time, it reduces their appetite and body weight, improves their sugar metabolism, and increases energy expenditure.
A new paper that appears in the journal eLife suggests that the hormone has a similar effect in primates such as monkeys and humans. This may mean that LCN2 could help people with obesity lose weight.
Obesity is an increasingly serious worldwide health concern. According to the World Health Organization (WHO), at least 2.8 million people die every year as a result of obesity or overweight.
This condition is also associated with other chronic health concerns, such as type 2 diabetes, coronary heart disease, stroke, cancer, and depression, among others.
Doctors typically class people as having overweight when they have a body mass index (BMI) of 25 or above, and they tend to class people as having obesity if they have a BMI of 30 or above.
Currently, it is difficult to reduce obesity because of researchers’ limited understanding of the body’s mechanisms that maintain a balance between weight, energy intake, and energy use.
For example, when people who have had obesity for a long time lose weight, their bodies respond by slowing down their metabolism, which can ultimately lead to weight regain.
In general, diet- and exercise-based weight loss programs tend to work in the short term, while known pharmacological therapies raise safety concerns and have a limited effect.
Lead study author Dr. Peristera-Ioanna Petropoulou and colleagues believe that conducting further research into LCN2 may lead to a new way of reducing obesity.
During the study, Dr. Petropoulou was a postdoctoral research scientist at Columbia University Irving Medical Center in New York City, NY. She is now affiliated with the Helmholtz Diabetes Center at Helmholtz Zentrum München in Germany.
“LCN2 acts as a signal for satiety after a meal, leading mice to limit their food intake, and it does this by acting on the hypothalamus within the brain. We wanted to see whether LCN2 has similar effects in humans, and whether a dose of it would be able to cross the blood-brain barrier.”
– Dr. Peristera-Ioanna Petropoulou
How does LCN2 work?
LCN2 is a hormone produced in the bone cells of mammals, including humans.
The study authors analyzed the data of four previous studies involving people with a “normal weight,” people with overweight, people with obesity, and people with severe obesity. These demonstrated that the concentration of LCN2 in the blood of people with a normal weight rises after eating.
It reaches the highest levels around 45–60 minutes after the meal, and during the same period, people’s hunger levels tend to decrease.
Some people with overweight had a smaller initial rise in LCN2 concentration followed by a drop, and their sensation of fullness after consuming a meal was weaker.
The LCN2 levels of people with obesity decreased after eating. As a result, researchers believe that the regulation of LCN2 may be key to understanding and potentially reducing obesity.
LCN2 in mice and monkeys
Previous research has suggested that injecting LCN2 into lean mice and those with obesity reduced their appetite by activating receptors in the hypothalamus. This is a part of the brain that is responsible for the feeling of hunger and fullness.
Researchers have identified mutations of the receptors that LCN2 works on as a common cause of obesity.
LCN2 works in mice by crossing the blood-brain barrier. This is a barrier formed through the unique properties of the smallest blood vessels of the central nervous system. Its role is to regulate which molecules can pass from the bloodstream into the brain.
It ensures that the brain receives the molecules required for its functioning, and it also serves as a border that protects the brain from harmful agents.
The new study suggests that LCN2 is capable of crossing the blood-brain barrier and binding to the hypothalamus in monkeys. This may mean that it might work the same way in humans.
“We have shown that LCN2 crosses to the brain, makes its way to the hypothalamus, and suppresses food intake in non-human primates,” says senior study author Prof. Stavroula Kousteni.
The study also suggests that, like those of mice, monkeys’ appetites decrease if they receive LCN2.
In the study, one group of monkeys received LCN2, and another group received a saline solution for a week. The food consumption of the LCN2-treated monkeys decreased by 27%, while it decreased by 25% in the monkeys who received the saline solution.
The researchers observed weight loss even over a short period of time. However, other observed metabolic parameters did not change in any significant way.
Because of the few monkeys involved in the study, however, further research will be required to conclusively prove the results.
Is it safe?
An important question of the study was whether or not giving LCN2 to primates has any dangerous side effects.
The researchers regularly collected and analyzed blood samples from the monkeys, looking for the usual indicators of liver and kidney injury or toxicity, but they found no significant changes in those markers.
This suggests that LCN2 appears to be a safe way of reducing the sensation of hunger. As a result, it may have the potential of becoming a new method to achieve and maintain weight loss.
The study authors believe that further, larger-scale research into how BMI, food composition, and other factors influence the response to LCN2 in humans is required.
However, these initial results indicate that scientists could develop an LCN2-based intervention in the future to safely reduce overweight and obesity.
“Our results show that the hormone can curb appetite with negligible toxicity and lay the groundwork for the next level of LCN2 testing for clinical use,” concludes Prof. Kousteni.
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