Hormone that switches off hunger could treat obesity

Anti-Obesity Drug May Allow You To Lose Weight Without Changing Food Intake

A hormone that can make mice feel full and keep them from overeating has shown similar results in humans, a new study found.

The hormone, called Lipocalin-2, could be used as a treatment in people with obesity whose natural signals for feeling full no longer work.

LCN2 is found naturally in mice and humans and is mainly produced by bone cells. Studies in mice have shown that giving LCN2 to the animals long term reduces how much they eat and prevents weight gain, without slowing down their metabolism.

“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,” said lead author Peristera-Ioanna Petropoulou, who was a postdoctoral research scientist at Columbia University Irving Medical Center at the time the study was carried out. “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.”

For their study, the scientists analyzed data from four studies in the United States and Europe. The studies involved people who were normal weight, overweight or obese. After a night of fasting, each participant was given a meal, with researchers measuring the amount of LCN2 in their blood before and after eating.

The researchers found increased LCN2 levels in people of normal weight and decreased levels in those who were overweight or obese. Based on levels, the participants were grouped as responders (higher levels) and nonresponders (no increase in LCN2 levels).

Nonresponders, who showed no increase in LCN2 after a meal, tended to have a larger waist circumference and higher markers of metabolic disease — including BMI, body fat, increased blood pressure and increased blood glucose.

Researchers also found that people who had lost weight after gastric bypass surgery had a restored sensitivity to LCN2 — changing their status from nonresponders before their surgery, to responders afterward.

After verifying that LCN2 can cross into the brain, the team 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% decrease in food intake compared with that before treatment within a week, and the monkeys also ate 21% less than their counterparts who were treated only with saline. Moreover, after only 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,” concludes senior author Stavroula Kousteni, Professor of Physiology and Cellular Biophysics at Columbia University Irving Medical Center. “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.”

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