title: Hormonal, hypothalamic and striatal responses to reduced body weight gain are attenuated in anorectic rats bearing small tumors.
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.
authors.affiliation: CNRS UMR 5226-INRA 1286, Université de Bordeaux, France.
authors.forename: Line
authors.initials: L
authors.lastname: Pourtau
authors.forename: Susan
authors.initials: S
authors.lastname: Leemburg
authors.forename: Pascale
authors.initials: P
authors.lastname: Roux
authors.forename: Thierry
authors.initials: T
authors.lastname: Leste-Lasserre
authors.forename: Patricia
authors.initials: P
authors.lastname: Costaglioli
authors.forename: Bertrand
authors.initials: B
authors.lastname: Garbay
authors.forename: Guillaume
authors.initials: G
authors.lastname: Drutel
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Konsman
mesh_terms: D000222:Adaptation, Physiological; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D001479:Basal Ganglia / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D002100:Cachexia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D054834:Lipocalins / Q000378:metabolism; D008113:Liver Neoplasms / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D016555:Matched-Pair Analysis; D009374:Neoplasms, Experimental / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D058748:Pain Perception / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011915:Rats, Inbred BUF; D013116:Spinal Cord / Q000378:metabolism; D015431:Weight Loss / Q000502:physiology
chemical_list: D054369:Agouti-Related Protein; D016207:Cytokines; D054439:Ghrelin; D020738:Leptin; D054834:Lipocalins; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase