Obesity accelerates cognitive decline by aggravating mitochondrial dysfunction, insulin resistance and synaptic dysfunction under estrogen-deprived conditions

At week eight, brain insulin resistance, mitochondrial dysfunction, and cognitive impairment were observed in female rats fed a high-fat diet after estrogen deprivation.

• Chronic high-fat diet consumption may lead to obesity and peripheral insulin resistance.
• Increased brain oxidative stress and hippocampal synaptic dysfunction were noted by week eight in estrogen-deprived rats on a high-fat diet.
• Brain insulin resistance and mitochondrial dysfunction developed earlier in high-fat diet groups compared to those on a normal diet.
• Cognitive impairment was linked to both estrogen deprivation and high-fat diet consumption.
• The combination of estrogen deprivation and a high-fat diet may exacerbate cognitive decline.

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