In Mice, One Gut Switch Pushes Fat and Inflammation in Opposite Directions

Researchers at the Scripps Research Institute and the University of California, Los Angeles report that a single receptor in the gut sets how much fat the intestine releases into the bloodstream after a meal, and that pushing it one way or the other produces opposite effects. The experiments were done in mice.

The receptor is the neurokinin-2 receptor, or NK2R, which picks up nerve messenger signals called tachykinins. In the eLife paper, published Oct. 5, 2026, Pedro A. Perez, Supriya Srinivasan and colleagues suggest that drugs built to switch NK2R on, or to block it, could be worth testing against metabolic disease and inflammatory bowel disease, with the choice depending on the condition and on sex.

The authors report that deleting the NK2R gene, or blocking the receptor with a drug, raised blood fat after a meal and left more fat stored in the intestine. A drug that switched the receptor on did the reverse: the gut sent out less fat, body fat fell, and blood sugar control improved in mice made obese by diet.

In animals lacking the receptor, gene activity for handling fat was turned up while immune pathways were turned down, and the mix of secretory cells in the gut lining shifted differently in males and females. Males without NK2R were partly protected from colitis, an inflammation of the colon.

The receptor also shaped the mix of bacteria in the animals' feces, varying with both their genetics and their diet.

The paper's own account of the field is that nerve-signal control of fat metabolism is shared across species and increasingly tied to metabolic disease, while the mechanisms at the level of individual receptors have stayed unclear. The paper is open access under a Creative Commons license.