Green tea catechin EGCG attenuates hippocampal atrophy and cognitive impairment in obesity via autophagy signaling.

Obesity is prevalent and linked to cognitive impairment via hippocampal atrophy and insulin resistance. Here, we investigated whether the primary catechin of green tea, epigallocatechin‑3‑gallate (EGCG), could attenuate this neuropathology. Epidemiological analysis of UK Biobank adults with obesity provided an initial clue, showing a positive linear trend between green tea intake and hippocampal volume (p = 0.07). To elucidate the underlying mechanisms, we administered a human‑achievable dose of EGCG (50 mg/kg) to high‑fat diet-fed mice. EGCG treatment significantly reduced body weight and inflammatory signaling while improving insulin sensitivity, attenuating hippocampal atrophy, and mitigating cognitive deficits. Mechanistically, EGCG rescued synaptic structural integrity by suppressing the pro-inflammatory JNK pathway, restoring hippocampal insulin signaling (IRS1/Akt), and stimulating neuronal autophagy through the AMPK/mTOR/ULK1 axis. Together, these data provide translational evidence that EGCG counteracts obesity-linked neurodegeneration by linking metabolic health to hippocampal integrity through the inflammation-insulin-autophagy axis, motivating dietary trials to mitigate cognitive impairment.