Environmental Enrichment Normalizes Metabolic Function in the Murine Model of Prader-Willi Syndrome Magel2-Null Mice

Prader-Willi syndrome (PWS) is a rare genetic disease that causes developmental delays, intellectual impairment, constant hunger, obesity, endocrine dysfunction, and various behavioral and neuropsychiatric abnormalities. Standard care of PWS is limited to strict supervision of food intake and GH therapy, highlighting the unmet need for new therapeutic strategies. Environmental enrichment (EE), a housing environment providing physical, social, and cognitive stimulations, exerts broad benefits on mental and physical health. Here we assessed the metabolic and behavioral effects of EE in the Magel2-null mouse model of PWS. EE initiated after the occurrence of metabolic abnormality was sufficient to normalize body weight and body composition, reverse hyperleptinemia, and improve glucose metabolism in the male Magel2-null mice. These metabolic improvements induced by EE were comparable to those achieved by a hypothalamic brain-derived neurotrophic factor gene therapy although the underlying mechanisms remain to be determined. These data suggest biobehavioral interventions such as EE could be effective in the treatment of PWS-related metabolic abnormalities.