Possible role of creatine concentrations in the brain in regulating appetite and weight.
Cobaltic protoporphyrin IX (CoPP) is a synthetic heme analog which can elicit profound and prolonged decreases in appetite and body weight in several different animal species. Intracerebroventricular administration of CoPP in rats was found, by differential display and confirmed by Real-Time PCR, to result in an increase in expression of the creatine transporter when compared to vehicle-treated fed or vehicle-treated fasted control animals. In situ hybridization studies showed that creatine transporter mRNA concentrations were increased in several areas of the brain involved in the regulation of food intake, but creatine concentrations were decreased in hypothalamic homogenates in CoPP-treated animals compared to controls. Intracerebroventricular administration of beta-guanidinopropionic acid, a compound known to decrease intracellular creatine concentration by competition for uptake, resulted in decreased food intake and body weight and increased Fos expression in the hypothalamus. Taken together, these findings suggest that creatine concentrations in the brain may play a role in regulating food intake and body weight.
Galbraith
Richard A
RA
Department of Medicine, University of Vermont, C209 Given Building, 89 Beaumont Avenue, Burlington, VT 05405, USA. richard.galbraith@uvm.edu
Furukawa
Masaru
M
Li
Muyao
M
D000704:Analysis of Variance; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003401:Creatine / Q000235:genetics / Q000378:metabolism*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007276:Injections, Intraventricular / Q000379:methods; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D011524:Protoporphyrins; C028025:protoporphyrin IX; D003401:Creatine