Eating extra servings typically shows up on the scale later, but how this happens has not been clear. A new study published in the Journal of Clinical Investigation by a multi-institutional team led by researchers at Baylor College of Medicine reveals a previously unknown gut-brain connection that helps explain how those extra servings lead to weight gain. Mice consuming a high-fat diet show increased levels of gastric inhibitory polypeptide (GIP), a hormone produced in the gut that is involved in managing the body’s energy balance. The study reports that the excess GIP travels through the blood to the brain where it inhibits the action of leptin, the satiety hormone; consequently, the animals continue eating and gain weight. Blocking the interaction of GIP with the brain restores leptin’s ability to inhibit appetite and results in weight loss in mice.

Further experiments showed that if the animals were genetically engineered to be leptin deficient, then the treatment with the specific monoclonal antibody did not reduce appetite and weight in obese mice, indicating that GIP in the brain acts through leptin signaling. In addition, the researchers identified intracellular mechanisms involved in GIP-mediated modulation of leptin activity. Although more research is needed, the researchers speculate that these findings might one day be translated into weight loss strategies that restore the brain’s ability to respond to leptin by inhibiting the anti-leptin effect of GIP.