Fermentation-Induced Phenolic Remodeling of Aronia melanocarpa Alleviates Obesity-Induced Cognitive Dysfunction Associated With Coordinated Modulation of the AMPK/NF-κB/BDNF Axis and BBB Integrity.

Obesity-induced cognitive decline involves chronic inflammation and neuronal dysfunction. This study investigated the mechanistic associations of probiotic-fermented Aronia melanocarpa extract (LAB-A) on metabolic and cognitive dysfunction in high-fat diet (HFD)-fed mice. Fermentation doubled total polyphenol content and increased aglycones like quercetin and eriodictyol. LAB-A attenuated microglial neuroinflammation by inhibiting NF-κB translocation (94.4% reduction, p < 0.05) and protected neurons from apoptosis by reducing the BAX/BCL-2 ratio (89.3%, p < 0.05). In HFD-fed mice, LAB-A significantly reduced weight gain and improved lipid/hepatic profiles (p < 0.05). Behaviorally, LAB-A significantly ameliorated cognitive deficits, improving recognition and spatial memory (p < 0.05). At the molecular level, LAB-A suppressed hippocampal NF-κB, restored AMPKα phosphorylation, and markedly upregulated BDNF (∼11.0-fold, p < 0.05). These changes were accompanied by reinforced blood-brain barrier (BBB) integrity, as evidenced by a 3.1-fold increase in Occludin (p < 0.05). Fermentation enhances the bioactivity of Aronia by increasing aglycone-type phenolics. LAB-A effectively mitigates obesity-related metabolic and cognitive dysfunction, associated with coordinated modulation of the AMPKα/NF-κB/BDNF axis and reinforcement of BBB integrity, highlighting its potential as a functional food ingredient for obesity-associated neuroprotection.