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Increased feeding in fatty Zucker rats by the thiazolidinedione BRL 49653 (rosiglitazone) and the possible involvement of leptin and hypothalamic neuropeptide Y
Author(s) -
Wang Qiong,
Dryden Simon,
Frankish Helen M.,
Bing Chen,
Pickavance Lucy,
Hopkins David,
Buckingham Robin,
Williams Gareth
Publication year - 1997
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.0701535
Subject(s) - medicine , endocrinology , neuropeptide y receptor , leptin , insulin , corticosterone , rosiglitazone , thiazolidinedione , weight gain , chemistry , hormone , diabetes mellitus , biology , neuropeptide , body weight , obesity , type 2 diabetes , receptor
1 The thiazolidinedione BRL 49653 (rosiglitazone) induces hyperphagia and weight gain in obese, insulin‐resistant fatty Zucker rats but not in lean insulin‐sensitive rats. We investigated whether these responses might involve neuropeptide Y (NPY), leptin and insulin. 2 BRL 49653 (1 mg kg −1 day −1 , orally) was given for 7 or 20 days to fatty and lean Zucker and Wistar rats. 3 In lean rats of either strain, BRL 49653 had no effect on food intake, body weight, plasma insulin and corticosterone, NPY or NPY mRNA levels. 4 Fatty rats given BRL 49653 showed a 30% increase in food intake and accelerated body weight gain (both P <0.01) after 7 and 20 days, but without significant changes in regional hypothalamic NPY or NPY mRNA levels. 5 Plasma leptin levels were twice as high in untreated fatty Zucker rats as in lean rats ( P <0.01), but were unaffected by BRL 49653 given for 20 days. However, BRL 49653 reduced insulin levels by 42% and increased corticosterone levels by 124% in fatty rats (both P <0.01). 6 Hyperphagia induced in fatty Zucker rats by BRL 49653 does not appear to be mediated by either a fall in circulating leptin levels or increased activity of hypothalamic NPYergic neurones. The fall in plasma insulin and/or rise in corticosterone levels during BRL 49653 treatment may be involved, consistent with the postulated role of these hormones in the control of food intake.