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Sibutramine reduces feeding, body fat and improves insulin resistance in dietary‐obese male Wistar rats independently of hypothalamic neuropeptide Y
Author(s) -
Brown Michael,
Bing Chen,
King Peter,
Pickavance Lucy,
Heal David,
Wilding John
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704030
Subject(s) - sibutramine , endocrinology , medicine , neuropeptide y receptor , insulin resistance , leptin , anorectic , obesity , diet induced obese , insulin , serotonin , orlistat , weight loss , body weight , neuropeptide , receptor
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.British Journal of Pharmacology (2001) 132 , 1898–1904; doi: 10.1038/sj.bjp.0704030