Original Article
International Journal of Obesity (2008) 32, 639–647; doi:10.1038/sj.ijo.0803759; published online 4 December 2007
Lack of starvation-induced activation of AMP-activated protein kinase in the hypothalamus of the Lou/C rats resistant to obesity
N Taleux1,2, I De Potter1, C Deransart3, G Lacraz2, R Favier2, X M Leverve2, L Hue1,4 and B Guigas1,4
- 1Université catholique de Louvain and Institute of Cellular Pathology, Hormone and Metabolic Research Unit, Brussels, Belgium
- 2Bioénergétique Fondamentale et Appliquée INSERM U 884, Université J. Fourier, Grenoble, France
- 3UMR 836 Inserm-UJF-CEA 'Grenoble - Institut des Neurosciences', Grenoble, France
Correspondence: Dr B Guigas, Department of Molecular Cell Biology, Leiden University Medical Center, Postzone S1-P, Postbus 9600, Leiden 2300 RC, The Netherlands. E-mail: b.guigas@lumc.nl
4These authors contributed equally and must be considered as joined last authors.
Received 2 May 2007; Revised 25 September 2007; Accepted 21 October 2007; Published online 4 December 2007.
Abstract
Objective:
The AMP-activated protein kinase (AMPK) is involved in the control of food intake by the hypothalamus. The aim of this work was to investigate if modification of hypothalamic AMPK regulation could be related to the spontaneous food restriction of Lou/C rats, a strain resistant to obesity exhibiting a 40% reduction in caloric intake compared with their lean Wistar counterparts.
Design:
Three-month-old male Lou/C rats were compared with age-matched male Wistar rats in both fed ad libitum and 24-h food deprivation state.
Measurements and results:
We first confirmed that starvation activated both isoforms of AMPK catalytic 
subunits and enhanced the phosphorylation state of its downstream targets acetyl-CoA carboxylase and elongation factor 2 in the hypothalamus of Wistar rats. These changes were not observed in the hypothalamus of Lou/C rats. Interestingly, the starvation-induced changes in hypothalamic mRNA levels of the main orexigenic and anorexigenic neuropeptides were also blunted in the Lou/C rats. Analysis of the concentrations of circulating substrates and hormones known to regulate hypothalamic AMPK indicated that the starvation-induced changes in ghrelin, adiponectin and leptin were not observed in Lou/C rats. Furthermore, an increased phosphorylation state of signal transducer and activator of transcription 3 (STAT3), which admittedly mediates leptin signaling, was evidenced in the hypothalamus of the starved Lou/C rats, as well as modifications of expression of the leptin-sensitive genes suppressor of cytokine signaling-3 and stearoyl-coenzyme A desaturase 1. In addition, despite reduced leptin level in fed Lou/C rats, the phosphorylation state of hypothalamic STAT3 remained similar to that found in fed Wistar rats, an adaptation that could be explained by the concomitant increase in ObRb leptin receptor mRNA expression.
Conclusion:
Activation of hypothalamic AMPK by starvation, which stimulates food intake through changes in (an)orexigenic neuropeptides in the normal rats, was not observed in the spontaneously hypophagic Lou/C rats.
Keywords:
AMPK, hypothalamus, food intake, leptin, ghrelin, adiponectin
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