Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors.
Brain, Behavior, and Immunity. 2011-05-01; 25(4): 777-786
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1. Brain Behav Immun. 2011 May;25(4):777-86. doi: 10.1016/j.bbi.2011.02.004. Epub
2011 Feb 18.
Hormonal, hypothalamic and striatal responses to reduced body weight gain are
attenuated in anorectic rats bearing small tumors.
Pourtau L(1), Leemburg S, Roux P, Leste-Lasserre T, Costaglioli P, Garbay B,
Drutel G, Konsman JP.
(1)CNRS UMR 5226-INRA 1286, Université de Bordeaux, France.
Lack of compensatory or even reduced food intake is frequently observed in
weight-losing cancer patients and contributes to increased morbidity and
mortality. Our previous work has shown increased transcription factor expression
in the hypothalamus and ventral striatum of anorectic rats bearing small tumors.
mRNA expression of molecules known to be involved in pathways regulating appetite
in these structures was therefore assessed in this study. Given that pain,
pro-inflammatory cytokines and metabolic hormones can modify food intake, spinal
cord cellular activation patterns and plasma concentrations of cytokines and
hormones were also studied. Morris hepatoma 7777 cells injected subcutaneously in
Buffalo rats provoked a 10% lower body weight and 15% reduction in food intake
compared to free-feeding tumor-free animals 4 weeks later when the tumor
represented 1-2% of body mass. No differences in spinal cord activation patterns
or plasma concentration of pro-inflammatory cytokines were observed between
groups. However, the changes in plasma ghrelin and leptin concentrations found in
food-restricted weight-matched rats in comparison to ad libitum-fed animals did
not occur in anorectic tumor-bearing animals. Real-time PCR showed that
tumor-bearing rats did not display the increase in hypothalamic agouti-related
peptide mRNA observed in food-restricted weight-matched animals. In addition,
microarray analysis and real-time PCR revealed increased ventral striatal
prostaglandin D synthase expression in food-restricted animals compared to
anorectic tumor-bearing rats. These findings indicate that blunted hypothalamic
AgRP mRNA expression, probably as a consequence of relatively high leptin and low
ghrelin concentrations, and reduced ventral striatal prostaglandin D synthesis
play a role in maintaining cancer-associated anorexia.
Copyright © 2011 Elsevier Inc. All rights reserved.
PMID: 21334429 [Indexed for MEDLINE]