Vagal neuron expression of the microbiota-derived metabolite receptor, free fatty acid receptor (FFAR3), is necessary for normal feeding behavior.
Level 5 - mechanism / opinion, no new human data
Preclinical animal knockout and ex vivo tissue study without human data.
PubMed 34626852 · doi:10.1016/j.molmet.2021.101350
What was done
Researchers developed a mouse model with a Cre-recombinase-driven targeted deletion of the free fatty acid receptor 3 (*Ffar3*) in vagal neurons. They evaluated feeding behavior in control and vagal-FFAR3 knockout (KO) mice under fasting/refeeding paradigms, high-fat Western diet feeding, and oral propionate supplementation. In addition, *ex vivo* organotypic vagal cultures and sequencing were used to investigate signaling cross-talk downstream of propionate-induced FFAR3 activation.
What was found
The abstract does not report exact numerical values or sample sizes. Vagal-FFAR3 KO mice showed increased meal size across both male and female mice, along with increased total food intake during fasting/refeeding and Western diet feeding compared to controls. Furthermore, the normal appetite-suppressing (anorectic) effect of propionate supplementation was lost in the vagal-FFAR3 KO mice. Mechanistic assays revealed that FFAR3 signaling intersects with cholecystokinin (CCK) and leptin receptor pathways to regulate food intake.
Why it matters
This study identifies vagal sensory FFAR3 as a critical molecular transducer connecting gut microbiota-derived short-chain fatty acids (specifically propionate) to central satiety signaling and appetite control.
Limits
The study was conducted entirely in rodent models and *ex vivo* tissue cultures, so direct applicability to human feeding physiology remains unverified. The abstract does not provide specific cohort sizes, exact effect sizes, or variance estimates.
Cited by
- supports Gut bacteria ferment dietary fiber to produce short-chain fatty acids, which signal to the brain through the vagus nerve and the bloodstream.