ICEECE2012 Poster Presentations Neuroendocrinology (83 abstracts)
Intracerebroventricular administration of metformin inhibits ghrelin-induced hypothalamic AMP-kinase signalling and food intake
D. Stevanovic 1 , K. Janjetovic 1, , M. Misirkic 1, , L. Vucicevic 1, , M. Sumarac-Dumanovic 1 , D. Micic 1 , V. Starcevic 1 & V. Trajkovic
1School of Medicine, University of Belgrade, Belgrade, Serbia; 2University of Belgrade, Belgrade, Serbia.
The antihyperglycaemic drug metformin reduces food consumption through mechanisms that are not fully elucidated. The present study investigated the effects of intracerebroventricular administration of metformin on food intake and hypothalamic appetite-regulating signalling pathways induced by the orexigenic peptide ghrelin. Rats were injected intracerebroventricularly with ghrelin (5 μg), metformin (50, 100 or 200 μg), AICAR (25 μg) and L-leucine (1 μg) in different combinations. Food intake was monitored during the next 4 h Hypothalamic activation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), Raptor, mammalian target of rapamycin (mTOR) and P70 S6 kinase 1 (S6K) after 1 h of treatment was analyzed by immunoblotting. Obtained results showed that metformin in a dose-dependent manner suppressed the increase in food consumption induced by ICV ghrelin. Ghrelin increased phosphorylation of hypothalamic AMPK and its targets ACC and Raptor, which was associated with the reduced phosphorylation of mTOR. The mTOR substrate S6K was activated by ICV ghrelin despite the inhibition of mTOR. Metformin treatment blocked ghrelin-induced activation of hypothalamic AMPK/ACC/Raptor and restored mTOR activity without affecting S6K phosphorylation. Metformin also reduced food consumption induced by the AMPK activator AICAR, while ghrelin-triggered food intake was inhibited by the mTOR activator L-leucine. Thus, metformin could reduce food intake by preventing ghrelin-induced AMPK signalling and mTOR inhibition in the hypotalamus.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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