Impact of type 2 diabetes and high-intensity interval exercise on neurogenesis, angiogenesis, and the accumulation of lipid droplets in the hippocampus

The risk of developing Alzheimer’s disease (AD) is doubled in individuals with type 2 diabetes (T2D). While the prevalence of both diseases increases globally, the T2D-AD link remains to be elucidated. Ectopic accumulation of lipids (lipotoxicity) is a known consequence of T2D and has lately been suggested as a driver for AD. Angiogenesis and adult neurogenesis are thought to be affected in both diseases. Physical exercise acts preventively against AD and T2D and has been shown to stimulate angiogenesis and neurogenesis. In this study, we exposed animals from the db/db mouse model of T2D to eight-weeks of high-intensity interval exercise (HIIT). In a series of immunohistochemical experiments of the hippocampus, we investigated the amount and distribution of lipid droplets (LDs), as well as levels of angiogenesis and adult neurogenesis. We found that microglia of diabetic animals had increased amounts of LDs compared to controls, and this was unaffected by HIIT. Furthermore, HIIT increased capillary density in the hippocampus in diabetic mice but not in their non-diabetic littermates. Contrarily, HIIT caused an increase in neurogenesis in the non-diabetic mice exclusively. Finally, we found no correlations between LD accumulation, angiogenesis, and neurogenesis, suggesting that these processes are independent of each other.