Obesity suppresses hippocampal neurogenesis and impairs memory and executive function in a weight and sex-specific manner.

There is a well-established link between a high-fat diet (HFD) as a cause of obesity, which, in addition to metabolic and cardiovascular pathology, is also associated with memory loss and cognitive decline. We investigated the conditional relationship between HFD, body weight, cognitive performance and adult hippocampal neurogenesis in male and female mice. The mice receiving HFD for three months were heavier and exhibited impaired long-term memory and diminished problem-solving ability in comparison to the groups on standard chow diet (SD). The severity of the cognitive impairment was dependent on their weight as shown by regressive analysis of the data. However, the HFD and increased body weight negatively affected the short-term spatial memory, a hippocampus-dependent task, only in male but not in female mice. Next, we compared the expression of Ki67 and DCX as markers for adult neurogenesis in the subgranular zone of the dentate gyrus of the dorsal hippocampus of mice on SD and HFD. The HFD reduced the densities of Ki67- and DCX-labeled cells only in male but not in the female mice. These results revealed that the cognitive impairment triggered by HFD was proportionate to the weight of the mice. However, the female mice preserved the rate of adult neurogenesis in the dentate gyrus and their cognitive functions in hippocampus-dependent tasks despite being susceptible to the deleterious effects of HFD in other cognitive domains.