Human and monkey research indicates that lipocalin-2 (LCN2), a hormone that plays a role in feeling satisfied after eating a meal, may be able to help individuals lose weight.
Previous studies have indicated that it decreases their appetite and body weight when mice obtain LCN2 over a period of time, enhances their sugar metabolism, and increases energy expenditure.
A recent paper that appears in the eLife journal indicates that in primates such as monkeys and humans, the hormone has a similar effect. This may mean that LCN2 could help to lose weight for people with obesity.
Obesity is a worldwide health issue that is increasingly extreme. At least 2.8 million people die each year as a result of obesity or excess weight, according to the World Health Organization (WHO).
Doctors generally classify patients as overweight when they have a body mass index (BMI) of 25 or higher, and if they have a BMI of 30 or higher, they tend to classify people as being obese.
Currently, obesity is difficult to minimize because of the limited understanding by researchers of the mechanisms of the body that maintain a balance between weight, energy consumption, and energy usage.
For instance, when individuals who have been obese for a long time lose weight, their bodies respond by slowing down their metabolism, which can eventually contribute to weight recovery.
In general, weight loss programs focused on diet and exercise appear to operate in the short term, whereas known pharmacological therapies pose questions about safety and have a limited impact.
Dr. Peristera-Ioanna Petropoulou, lead author of the study, and colleagues suggest that more research into LCN2 can lead to a new way to reduce obesity.
Dr. Petropoulou was a postdoctoral research scientist at the Irving Medical Center at Columbia University in New York City, NY during the research. She is now affiliated with the Helmholtz Diabetes Center in Germany at the Helmholtz Zentrum München.
“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 mammal bone cells, including in humans.
The authors of the report analyzed data from four previous studies involving individuals with “normal weight,” overweight individuals, individuals with obesity, and individuals with extreme obesity. They found that after feeding, the concentration of LCN2 in the blood of people with average weight increases.
About 45-60 minutes after the meal, it hits the highest levels, and during the same time, the hunger levels of people begin to decrease.
Some overweight individuals had a smaller initial increase in the concentration of LCN2 followed by a decrease, and their feeling of fullness was poorer after eating a meal.
After eating, the LCN2 levels of people with obesity declined. As a result, scientists conclude that LCN2 regulation could be important to understanding and potentially reducing obesity.
LCN2 in mice and monkeys
Previous studies indicated that by activating receptors in the hypothalamus, injecting LCN2 into lean mice and those with obesity decreased their appetite. This is a part of the brain responsible for the sense of fullness and hunger.
Scientists have identified receptor mutations that LCN2 acts on as a common cause of obesity.
In mice, LCN2 functions by breaching the blood-brain barrier. This is a barrier created by the special properties of the central nervous system‘s smallest blood vessels. Its function is to control which molecules are able to move into the brain from the bloodstream.
It ensures that the molecules required for its work are obtained by the brain, and it also serves as a border that protects the brain from harmful agents.
The new research indicates that in monkeys, LCN2 is able to cross the blood-brain barrier and bind to the hypothalamus. This could mean that in humans, it may function the same way.
“We have shown that in non-human primates, LCN2 crosses into the brain, makes its way to the hypothalamus, and suppresses food intake,” says Prof. Stavroula Kousteni, senior study author.
The study also shows that if they receive LCN2, the appetites of monkeys decrease, like those of mice.
One group of monkeys in the study received LCN2, and another group received a week-long saline solution. The food intake of the monkeys treated with LCN2 decreased by 27 percent, while in the monkeys who got the saline solution it decreased by 25 percent.
Also within a brief period of time, the researchers observed weight loss. Other metabolic parameters observed did not change in any significant way, however.
However, due to the few monkeys involved in the analysis, more studies would be required to prove the findings conclusively.
Is it safe?
A significant issue in the study was whether or not there were any dangerous side effects of giving LCN2 to primates.
Blood samples from the monkeys were routinely collected and examined by the researchers, searching for the normal signs of liver and kidney damage or toxicity, but no major changes in those markers were observed.
This indicates that it seems that LCN2 is a healthy way to reduce the sense of hunger. As a consequence, it could have the potential to become a new strategy for achieving and sustaining weight loss.
The research authors believe that further, larger-scale research is needed into how the response to LCN2 in humans is influenced by BMI, food composition, and other factors.
These initial findings, however, suggest that in the future scientists might establish an LCN2-based intervention to safely decrease overweight and obesity.
“Our findings show that with negligible toxicity, the hormone can curb appetite and lay the groundwork for the next level of clinical LCN2 testing,” Prof. Kousteni concludes.