Enhanced expressions of mRNA for neuropeptide Y and interleukin 1 beta in hypothalamic arcuate nuclei during adjuvant arthritis-induced anorexia in Lewis rats.
OBJECTIVE
Food intake is activated by hypothalamic orexigenic neuropeptide Y (NPY), which is mainly under the dual control of leptin and ghrelin. Rat adjuvant arthritis (AA), similarly as human rheumatoid arthritis, is associated with cachexia caused by yet unknown mechanisms. The aim of our study was to evaluate NPY expression in hypothalamic arcuate nuclei (nARC) under the conditions of AA-induced changes in leptin, ghrelin and adiponectin. Since IL-1beta is involved in the central induction of anorexia, we studied its expression in the nARC as well.


METHODS
AA was induced to Lewis rats using complete Freund's adjuvant. On days 12, 15 and 18 after complete Freund's adjuvant injection, the levels of leptin, adiponectin, ghrelin and IL-1beta were determined by RIA or ELISA. The mRNA expressions for NPY, leptin receptor (OB-R), ghrelin receptor (Ghsr) and IL-1beta were determined by TaqMan RT-PCR from isolated nARC.


RESULTS
In AA rats, decreased appetite, body mass and epididymal fat stores positively correlated with reduced circulating and epididymal fat leptin and adiponectin. Ghrelin plasma levels were increased. In nARC, mRNA for OB-R, Ghsr and NPY were overexpressed in AA rats. AA rats showed overexpression of mRNA for IL-1beta in nARC while circulating, and spleen IL-1beta was unaltered.


CONCLUSIONS
During AA, overexpression of orexigenic NPY mRNA in nARC along with enhanced plasma ghrelin and lowered leptin levels occur. Decreased food intake indicates a predominant effect of the anorexigenic pathway. Activated expression of IL-1beta in nARC suggests its role in keeping AA-induced anorexia in progress. The reduction in adiponectin may also contribute to AA-induced anorexia.
Stofkova
Andrea
A
Department of Normal, Pathological, and Clinical Physiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Haluzik
Martin
M
Zelezna
Blanka
B
Kiss
Alexander
A
Skurlova
Martina
M
Lacinova
Zdenka
Z
Jurcovicova
Jana
J
D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D000855:Anorexia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001066:Appetite / Q000502:physiology; D001069:Appetite Regulation / Q000502:physiology; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001168:Arthritis / Q000139:chemically induced / Q000150:complications; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D054439:Ghrelin / Q000097:blood / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics*; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D052242:Adiponectin; D054439:Ghrelin; D053583:Interleukin-1beta; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger