Hormone found could point to potential obesity treatment

A hormone that can suppress food intake and increase the feeling of fullness in mice has shown similar results in humans and non-human primates, according to a new study published in the journal eLife.

The hormone, called Lipocalin-2 (LCN2), could be used as a potential treatment in people with obesity whose natural signals for feeling full no longer work, the researchers said. LCN2 is mainly produced by bone cells and is found naturally in mice and humans. Studies in mice have shown that giving LCN2 to the animals long-term reduces their food intake and prevents weight gain, without leading to a slow-down in their metabolism.

For the study, researchers first analyzed data from four different studies of people in the United States and Europe who were either normal weight, overweight or living with obesity. The people in each study were given a meal after an overnight fast, and the amount of LCN2 in their blood before and after the meal was studied. The researchers found that in those who were of normal weight, there was an increase in LCN2 levels after the meal, which coincided with how satisfied they felt after eating, according to the study.

By contrast, in people who were overweight or had obesity, LCN2 levels decreased after a meal. Based on this post-meal response, the researchers grouped people as non-responders or responders. Non-responders, who showed no increase in LCN2 after a meal, tended to have a larger waist circumference and higher markers of metabolic disease, including body mass index, body fat, increased blood pressure, and increased blood glucose. Additionally, people who had lost weight after gastric bypass surgery were found to have a restored sensitivity to LCN2, changing their status from non-responders before their surgery, to responders afterwards, the researchers said.

Taken together, these results mirror those seen in mice, and suggest that this loss of post-meal LCN2 regulation is a new mechanism contributing to obesity and could be a potential target for weight-loss treatments.

After verifying that LCN2 can cross into the brain, the researchers explored whether treatment with the hormone might reduce food intake and prevent weight gain. To do this, they treated monkeys with LCN2 for a week. They saw a 28 percent decrease in food intake compared with that before treatment within a week, and the monkeys also ate 21 percent less than their counterparts who were treated only with saline. Moreover, after one week of treatment, measurements of body weight, body fat, and blood fat levels showed a declining trend in treated animals.

"We have shown that LCN2 crosses to the brain, makes its way to the hypothalamus and suppresses food intake in non-human primates," saod Stavroula Kousteni, senior author of the study and a professor of physiology and cellular biophysics at Columbia University Irving Medical Center, in a statement. "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."