Effects of voluntary exercise, diet, and selenium on hypothalamic adult neurogenesis.

Hypothalamic adult neurogenesis is implicated in energy homeostasis; however, the impact of physical exercise, particularly under high-fat diet (HFD) conditions, on this process remains unclear. To address this, we subjected mice to short-term and long-term voluntary running under control and HFD conditions. We show that long-term, but not short-term, running upregulates hypothalamic neurogenesis in Control mice. Conversely, short-term running rescues HFD-induced neurogenesis in the median eminence (ME), promoting the differentiation and survival of newly generated neurons. This rescue effect is absent with long-term running. Furthermore, we show that selenium mimics the effects of short-term running on ME neurogenesis and increases the activation and proliferation of hypothalamic adult neural stem cells, suggesting its role as a hypothalamic exerkine. Our findings indicate that voluntary exercise differentially influences adult neurogenesis in the hypothalamus compared to the hippocampus, with its neurogenic effects being modulated by diet, exercise duration, and regional differences within hypothalamic compartments.