Increased feeding in fatty Zucker rats by the thiazolidinedione BRL 49653 (rosiglitazone) and the possible involvement of leptin and hypothalamic neuropeptide Y

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Abstract
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. BRL 49653 (1 mg kg−1 day−1, orally) was given for 7 or 20 days to fatty and lean Zucker and Wistar rats. 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. Fatty rats given BRL 49653 showed a 30% increase in food intake and accelerated body weight gain (both PPP<0.01). 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.