A gut receptor controls fat absorption and inflammation
Your small intestine does more than digest food. New research shows that a receptor on gut cells simultaneously regulates fat absorption and immune responses, and that this dual role makes the gut vulnerable to inflammation when the balance is disrupted.
The gut wall contains receptors that receive signals from nerve compounds. One of them is the neurokinin-2 receptor (NK2R), which responds to tachykinins, a group of signaling molecules active in nerves and the gut. Until now, the specific role of NK2R in the intestine was unclear.
The researchers examined what happens when NK2R is switched off or activated, in mice and through pharmacological tools. They found that NK2R acts as a central switch controlling both fat absorption and immune responses. When NK2R was blocked, blood triglyceride levels rose more after meals and fat accumulated more in the gut wall. Activating NK2R had the opposite effect: less fat absorption, reduced fat around organs, and better blood sugar control in diet-induced obese mice.
Inflammation and sex differences
NK2R also influenced the risk of gut inflammation. Mice lacking NK2R were less susceptible to colitis, a chronic inflammation of the colon. That effect was sex-specific: male mice appeared more protected. The researchers found that NK2R changes the composition of mucus-producing cells in the gut wall, contributing to susceptibility to inflammation.
In addition, the composition of gut bacteria (microbiota) changed depending on whether NK2R was active and on the mice’s diet. This points to an interaction between neuropeptide signaling, gut cells, and intestinal bacteria.
Relevance for aging
This study, published in eLife, was conducted mainly in mice. Translation to humans remains uncertain. But the combination of fat metabolism and gut inflammation is relevant for longevity: both processes worsen with age and contribute to chronic disease. The researchers suggest NK2R as a therapeutic target, but clinical evidence is entirely lacking at this stage.
Search terms to explore further: neurokinin-2 receptor intestinal inflammation, chylomicron lipid absorption gut, neuropeptide metabolism gut epithelium