othalamic tissue, reducing neuronal AMPK activity. As well as in response to leptin, in the present study, we demonstrated that IL-6 alone reduced AMPK phosphorylation in the hypothalamus of rats. We also show that, IL-6 increased ATP levels and decreased Blocking effects of AICAR and Rapamycin on leptininduced anorexia We tested whether the i.c.v. administration of AICAR or Rapamycin, 60 minutes before the administration of leptin, prevents the anorexigenic effects of leptin. Leptin treatment markedly reduced 12-h food intake in both control and exercised groups, although leptin was much more effective in 25833960 exercised rats. AICAR or Rapamycin, at doses that do not alter ingestion, completely blocked the suppression of food intake induced by an i.c.v. injection of leptin . The i.c.v. administration of leptin to exercised rats pretreated with vehicle reduced AMPK and ACC phosphorylation in the hypothalamus by 63% and 60% respectively, compared with the control group. The administration of AICAR increased 
AMPK threonine and ACC serine Exercise and Leptin MedChemExpress Oritavancin (diphosphate) Action 8 Exercise and Leptin Action 9 Exercise and Leptin Action 10 Exercise and Leptin Action 11 Exercise and Leptin Action 12 Exercise and Leptin Action the AMP/ATP ratio in the hypothalamus, but the mechanisms by which IL-6 modulates the ATP levels require further investigations. A number of recent studies have shown that AMPK plays a key role in regulating both energy intake and expenditure. In peripheral tissues, such as skeletal muscle, activation of AMPK switches on energy producing pathways and switches off energy consuming pathways. In the hypothalamus, activation of AMPK leads to increased feeding, thereby increasing energy intake. Conversely, inhibition of AMPK in the hypothalamus reduces food intake. These dual functions of AMPK suggest that it may act to coordinate energy expenditure with energy intake. There is already some evidence that this may be the case in one situation. More recently, Gao and colleagues demonstrated that the hypothalamic ACC activation makes an important contribution to the anorexigenic effects of leptin that are mediated by AMPK. The aim of this study was to investigate 10980276 whether IL-6 could affect AMPK activity in the hypothalamus, thereby providing a potential mechanism for the coordination of energy expenditure and energy intake during, or following exercise. Beyond STAT3 activation, we detected changes in the hypothalamic AMPK activity in rats after i.c.v. infusion of IL-6; we show that, IL-6 markedly decreased phospho-AMPK abundance in the hypothalamus. In accordance with the reduction in AMPKthr172 phosphorylation, we observed that, after IL-6 administration, hypothalamic AMP:ATP ratio was decreased. Wallenius et al elegantly showed that long-term peripheral IL-6 treatment to Il62/2 mice caused a decrease in body weight. In addition to increasing energy expenditure, IL-6 may prevent obesity by inhibiting feeding as obese IL-62/2 mice had increased absolute food intake. However, central IL-6 treatment at the same dose that we used does not influence food intake in mice. In concordance with our results another study of the same group showed a reduced daily food intake over a two-week ICV treatment period with IL-6 in rats indicating a different pattern of response between rats and mice. The mTOR, an evolutionary conserved serine-threonine kinase, central to integrating similar signals to control food intake, has now emerged as a detector of hormonal and