RESUMEN
BACKGROUND/AIMS: Impaired insulin action is an early event in the pathogenesis of obesity and type 2-diabetes, and among the metabolic confounders in obese, hyperleptinaemia is constantly present; however its impact on insulin action in the brain and locomotor activity is unknown. METHODS: We examined insulin action by Western Blot analysis and glycogen synthesis in primary astrocytes and brain tissue and detected locomotion in C57BL/6 mice. The insulin-mediated desire to move was evaluated in healthy volunteers and correlated to leptin levels. RESULTS: Leptin treatment led to a significant decrease in insulin-mediated phosphorylation of the insulin receptor and Akt473 which was accompanied by a decline in glycogen synthesis in primary astrocytes and significantly decreased insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-2 in brain tissues of mice. Intracerebroventricular insulin failed to promote locomotion in the presence of elevated leptin levels. Lean human subjects reported an increase in the desire to move following insulin which failed in obese and there was an inverse correlation between the insulin-mediated desire to move and leptin levels. CONCLUSIONS: Our data suggest a crosstalk of leptin and insulin in the brain which leads to a decline in locomotor activity. This might represent a molecular mechanism in obese to inhibit physical activity.