The hormone LEAP2, which naturally blocks the “hunger” hormone ghrelin, is elevated in people with obesity, especially after eating – raising hopes for a treatment that could one day more effectively reduce appetite and, hence, obesity.

Scientists have been interested in the potential of LEAP2 (short for liver enriched antimicrobial peptide 2) for weight loss and appetite control since a 2018 study in mice and cell lines found the hormone attaches to the same brain receptors used by ghrelin, which stimulates hunger and increases food intake, weight gain, and blood glucose levels. By binding to those receptors, LEAP2 blocks the action of ghrelin.

Researchers at UT Southwestern and the Imperial College London evaluated how LEAP2 levels in the blood change in response to metabolic challenges. The new study, involving people enrolled in weight loss studies, showed that LEAP2 levels increase proportionately to body mass index and other markers of obesity.

The research points to LEAP2, a hormone produced in the liver and small intestine, as a natural brake on obesity and overeating, said Dr. Jeffrey Zigman, Professor of Internal Medicine at UT Southwestern and co-senior author of the paper. As LEAP2 levels go up with obesity, ghrelin levels go down. On the other hand, LEAP2 drops after weight loss from dieting or weight loss surgery.

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