Treadmill Running and Rutin Reverse High Fat Diet Induced Cognitive Impairment in Diet Induced Obese Mice.

OBJECTIVES: To determine the effects of treadmill exercise training and rutin intervention independently and in combination on key molecules involved in Alzheimer's disease (AD) pathology and cognitive function in diet induced obese (DIO) mice. METHODS: C57BL/6J mice were randomized into 5 groups: chow group, high fat diet group (HFD), HFD plus rutin intervention group (HR), HFD combined with treadmill running group (HE), HFD combined with treadmill running and rutin group (HRE). At the end of the intervention, Morris water maze test was conducted to assess hippocampal dependent, long term spatial learning and memory retention. Hippocampus and cortex were dissected and the protein expression of key molecules including insulin-degrading enzyme (IDE), Beta-secretase (BACE1), signal transducer and activator of transcription 3 (STAT3), cAMP-response element binding protein (CREB), post-synaptic density protein 95 (PSD-95) and synaptophysin were measured via western blotting. RESULTS: Exercise and rutin enhances HFD induced cognitive deficits in DIO mice. In the hippocampus, although HFD has no effect on IDE, BACE1, phosphorylation (p)-STAT3 and p-CREB, HR and HE group have elevated protein expression of IDE; meanwhile, p-CREB was elevated in the HE and HRE group. In the cortex, HFD led to induction in BACE1 and reduction in p-STAT3 and PSD95. Rutin or exercise reversed BACE1, p-STAT3 and PSD95 to normal levels. CONCLUSIONS: Treadmill running and rutin could improve HFD induced cognitive impairment, and p-STAT3, p-CREB, BACE1, IDE, and PSD95 are potential mediators involved in the protective effects of rutin or exercise against HFD induced cognitive dysfunction.