The adipocyte-secreted protein adiponectin (ADN) has anti-inflammatory and antidiabetic peripheral effects, similarly to exercise. Investigating a possible link between the effects of exercise and ADN on the brain in mice, Yau et al. showed that ADN can pass the blood–brain barrier and that running increased hippocampal ADN levels. Peripheral or central ADN administration reduced depression-like behaviour and promoted hippocampal cell proliferation. Running had the same effects, but not in mice lacking ADN. In vitro, the proliferation-promoting effect of ADN was mediated by ADN receptor 1. These data indicate that ADN mediates the neurogenesis-promoting and antidepressant effects of exercise.