Combined caloric restriction and exercise provides greater metabolic and neurocognitive benefits than either as a monotherapy in obesity with or without estrogen deprivation.

Neurodegeneration, as indicated by brain dysfunction and cognitive decline, is one of the complications associated with obesity and estrogen deprivation. Calorie restriction and exercise regimes improved brain function in neurodegenerative diseases. However, the comparative effects of a combination of calorie restriction with exercise, calorie restriction, and an exercise regime alone on brain/cognitive function in obesity with or without estrogen deprivation have not been investigated. Sixty female rats were fed a normal diet (ND) or a high-fat diet (HFD) for 27 weeks. At week 13, the ND-fed rats underwent a sham operation with sedentary lifestyle, HFD-fed rats were divided into two groups: each having either a sham operation (HFS) or ovariectomy (HFO). At week 20, HFD-fed rats in each group were divided into four subgroups undergoing either a sedentary lifestyle, calorie restriction, exercise regime or a combination of calorie restriction and exercise for 7 weeks. Insulin resistance, cognitive decline and hippocampal pathologies were found in both HFS and HFO rats. HFO rats had higher levels of insulin resistance and hippocampal reactive oxygen species levels than HFS rats. Calorie restriction decreased metabolic disturbance and hippocampal oxidative stress but failed to attenuate cognitive decline in HFS and HFO rats. Exercise attenuated metabolic/hippocampal dysfunctions, resulting in improved cognition only in HFS rats. Combined therapies restored brain function, and cognitive function in HFS and HFO rats. Therefore, a combination of calorie restriction with exercise is probably the greatest lifestyle modification to diminish the brain pathologies and cognitive decline in obesity with or without estrogen deprivation.