Dietary quercetin at 0.05% (w/w) reduced body weight gain and improved lipid profiles and cognitive performance in HFFD-fed obese mice, and was associated with gut microbiota remodeling (including increased Akkermansia muciniphila), restored intestinal barrier function, altered serum metabolites, reduced neuroinflammation, and activation of hippocampal PI3K/AKT/GSK3β signaling.
Quercetin supplementation significantly reduced body weight gain in mice fed a high-fat, high-fructose diet (HFFD).
Quercetin improved serum lipid abnormalities and cognitive performance in HFFD-fed mice.
Quercetin reshaped gut microbiota composition and notably increased Akkermansia muciniphila.
Quercetin regulated serum metabolite profiles, which the authors link to the gut microbiota changes.
Quercetin activated the hippocampal PI3K/AKT/GSK3β signaling pathway.
Quercetin suppressed neuroinflammation and inhibited abnormal tau phosphorylation and neuronal apoptosis.
The authors propose an integrated microbiota-gut-brain regulatory axis through which quercetin acts in obesity-related cognitive impairment.
This study in mice examined whether quercetin, a plant compound found in many fruits and vegetables, could protect against the memory and thinking problems that accompany obesity. Mice were fed a high-fat, high-fructose diet for 10 weeks, and some also received quercetin at 0.05% of their diet. Quercetin reduced weight gain, improved blood lipid levels, and improved cognitive performance. The researchers also looked at possible mechanisms. Quercetin changed the gut bacteria, including increasing Akkermansia muciniphila, and restored the integrity of the gut barrier. It also changed blood metabolites. In the brain's hippocampus, there was less inflammation, greater activity of the PI3K/AKT/GSK3β insulin-related signaling pathway (increases of about 46–50% in phosphorylated forms of these proteins), and less abnormal tau phosphorylation and nerve cell death. This research suggests quercetin may influence brain health in obesity through the gut-brain connection. However, the work was done in mice, and the abstract describes associations across multiple measures, so it does not show that quercetin would have the same effects in people. Human studies would be needed to test that.
Li W, Pei Y, Wang J, Zhang J, Zhang W, Jiang X, et al.. (2026). Quercetin Ameliorates Cognitive Impairment in Obese Mice by Activating the PI3K/AKT/GSK3β Signaling Pathway via the Microbiota-Gut-Brain Axis.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c04686