Sibutramine alters the central mechanisms regulating the defended body weight in diet-induced obese rats.
Chronic administration of sibutramine lowers body weight, presumably by altering brain monoamine metabolism. Here the effect of sibutramine on sympathoadrenal function (24-h urine norepinephrine and epinephrine levels) and arcuate nucleus (ARC) neuropeptide Y (NPY) and proopiomelanocortin (POMC) expression was assessed in diet-induced obese rats fed a low-fat diet. Chronic (10 wk) sibutramine [5 mg. kg(-1). day(-1) ip; rats fed ad libitum and injected with sibutramine (AS)] lowered body weight by 15% but only transiently (3-4 wk) reduced intake compared with vehicle-treated controls [rats fed chow ad libitum and injected with vehicle daily (AV)]. Other rats food restricted (RS) to 90% of the weight of AS rats and then given sibutramine restored their body weights to the level of AS rats when allowed libitum food intake. After reequilibration, RS rats were again energy restricted to reduce their weight to 90% of AS rats, and additional vehicle-treated rats (RV) were restricted to keep their body weights at the level of AS rats for 3 wk more. Terminally, total adipose depot weights and leptin levels paralleled body weights (AV > AS = RV > RS), although AS rats had heavier abdominal and lighter peripheral depots than RV rats of comparable body weights. Sibutramine treatment increased sympathetic activity, attenuated the increased ARC NPY, and decreased POMC mRNA levels induced by energy restriction in RV rats. Thus sibutramine lowered the defended body weight in association with compensatory changes in those central pathways involved in energy homeostasis.
Levin
B E
BE
Neurology Service, Department of Veterans Affairs New Jersey Health Care System, East Orange 07018, USA. levin@umdnj.edu
Dunn-Meynell
A A
AA
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D003503:Cyclobutanes / Q000494:pharmacology*; D002149:Energy Intake; D004837:Epinephrine / Q000652:urine; D005247:Feeding Behavior; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D020738:Leptin / Q000097:blood; D009478:Neuropeptide Y / Q000235:genetics; D009638:Norepinephrine / Q000652:urine; D009765:Obesity / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D001067:Appetite Depressants; D003503:Cyclobutanes; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; C058254:sibutramine; D009638:Norepinephrine; D004837:Epinephrine