Sibutramine reduces feeding, body fat and improves insulin resistance in dietary-obese male Wistar rats independently of hypothalamic neuropeptide Y.
We studied the effects of the novel noradrenaline and serotonin (5-HT) reuptake inhibitor sibutramine on feeding and body weight in a rat model of dietary obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY) neurones. Chow-fed and dietary-obese (DIO) male Wistar rats were given sibutramine (3 mg kg(-1) day(-1) p.o.) or deionized water for 21 days. Sibutramine decreased food intake throughout the treatment period in both dietary-obese rats (P<0.0001) and lean rats (P<0.0001). Weight gain was reduced so that final body weight was 10% lower in dietary-obese (P<0.005) and 8% lower in lean (P<0.05) rats versus their untreated controls. Plasma leptin concentration was lower in sibutramine-treated dietary-obese rats (P<0.05), and in treated lean rats (P<0.05). Using the homeostasis model assessment (HOMA) as a measure of insulin resistance, untreated DIO rats were significantly more insulin resistant than controls (P<0.005), and this was corrected by sibutramine treatment (P<0.05). Neither hypothalamic NPY mRNA nor NPY peptide levels in a number of hypothalamic nuclei were significantly altered by sibutramine compared to untreated controls. The hypophagic and anti-obesity effects of sibutramine in dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY neurones.
Brown
M
M
Department of Medicine, University of Liverpool, PO Box 147, Liverpool, L69 3GA.
Bing
C
C
King
P
P
Pickavance
L
L
Heal
D
D
Wilding
J
J
D000273:Adipose Tissue / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003503:Cyclobutanes / Q000494:pharmacology*; D004032:Diet; D005247:Feeding Behavior / Q000187:drug effects*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D001067:Appetite Depressants; D003503:Cyclobutanes; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; C058254:sibutramine