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Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors.
- Source :
-
Brain, behavior, and immunity [Brain Behav Immun] 2011 May; Vol. 25 (4), pp. 777-86. Date of Electronic Publication: 2011 Feb 18. - Publication Year :
- 2011
-
Abstract
- 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.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Adaptation, Physiological
Agouti-Related Protein genetics
Agouti-Related Protein metabolism
Analysis of Variance
Animals
Body Weight physiology
Cachexia etiology
Cachexia physiopathology
Carcinoma, Hepatocellular complications
Carcinoma, Hepatocellular physiopathology
Cytokines blood
Disease Models, Animal
Eating physiology
Gene Expression Regulation
Ghrelin genetics
Ghrelin metabolism
Immunohistochemistry
Intramolecular Oxidoreductases metabolism
Leptin genetics
Leptin metabolism
Lipocalins metabolism
Liver Neoplasms complications
Liver Neoplasms physiopathology
Male
Matched-Pair Analysis
Neoplasms, Experimental complications
Neoplasms, Experimental metabolism
Neoplasms, Experimental physiopathology
Pain Perception physiology
RNA, Messenger analysis
Rats
Rats, Inbred BUF
Spinal Cord metabolism
Weight Loss physiology
Appetite Regulation physiology
Basal Ganglia metabolism
Cachexia metabolism
Carcinoma, Hepatocellular metabolism
Hypothalamus metabolism
Liver Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2139
- Volume :
- 25
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Brain, behavior, and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 21334429
- Full Text :
- https://doi.org/10.1016/j.bbi.2011.02.004