Insulin differently modulates hypothalamic mitochondrial energy metabolism in fed or fasted mice: Involvement in food intake regulation?

0195-6663 doi: DOI: 10.1016/j.appet.2008.04.119In hypothalamus, mitochondria have been demonstrated to be involved in nutrients sensing but little is known concerning a mitochondrial insulin effect. The aim of our studywas thus to determine, in mice, whether (i) insulin may modulate mitochondrial functions and (ii) this effect varies according to metabolic state. O2 consumption, measured by oxygraphy in fresh hypothalamus explants was similar in fed and fasted mice on glutamate whereas it was lower in fasted mice on succinate. Whatever the metabolic state of the mice, insulin (3 nM) increased O2 consumption with glutamate. By contrast, insulin increased O2 consumption with succinate only in fasted mice. This increase allows to restore O2 consumption which was observed in fed mice in basal condition thus suggesting that insulin might improve free fatty acids utilisation in fasted mice. In in vivo experiments, third ventricular insulin injection strongly inhibits food intake, in fed mice, as already described.However, this effectwas not observed with similar insulin concentration (3 nM)in fasted mice. Experiments are currently under investigation in order to assess insulin effect on mitochondrial products and to establish a link between the level of these products and food intake regulation. Altogether these data demonstrate that the effects of insulin on mitochondrial function in hypothalamus and on food intake vary according to the metabolic state. doi:10.1016/j.appet.2008.04.12