Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors
Leptin
0301 basic medicine
Cachexia
Carcinoma, Hepatocellular
[SDV]Life Sciences [q-bio]
Hypothalamus
610
Basal Ganglia
Eating
03 medical and health sciences
Animals
Agouti-Related Protein
2. Zero hunger
Analysis of Variance
0303 health sciences
Appetite Regulation
Body Weight
Liver Neoplasms
Adaptation, Physiological
Immunohistochemistry
Ghrelin
Lipocalins
3. Good health
[SDV] Life Sciences [q-bio]
Intramolecular Oxidoreductases
Disease Models, Animal
Gene Expression Regulation
Cytokines
DOI:
10.1016/j.bbi.2011.02.004
Publication Date:
2011-02-19T04:52:32Z
AUTHORS (8)
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.
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