Gut-Brain Circuits for Fat Preference – Nature

The perception of fat evokes strong appetitive and consummatory responses¹. Here we show that fat stimuli can induce behavioural attraction even in the absence of a functional taste system^2,3. We demonstrate that fat acts post-ingestively via the gut-brain axis to drive preference for fat. Using single-cell data, we identified the vagal neurons responding to intestinal delivery of fat, and showed that genetic silencing of this gut-to-brain circuit abolished the development of fat preference. Next, we compared the gut-to-brain pathways driving preference for fat versus sugar⁴, and uncovered two parallel systems, one functioning as a general sensor of essential nutrients, responding to intestinal stimulation with sugar, fat and amino acids, while the other is activated only by fat stimuli. Lastly, we engineered animals lacking candidate receptors detecting the presence of intestinal fat, and validated their role as the mediators of gut-to-brain fat-evoked responses. Together, these findings revealed distinct cells and receptors using the gut-brain axis as a fundamental conduit for the development of fat preference.