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1 Division of Biological
Sciences: Neurobiology,
Neuropeptides play an important role in the integration of dietary signals. Cholecystokinin (CCK) has been implicated in regulating ingestive behavior, particularly satiety. The primary objective of this study was to examine whether the hyperphagia characteristic of obese (fa/fa) rats involves impaired neural CCK secretion. Dynamic release of CCK at the hypothalamic paraventricular nucleus (PVN) of age-matched lean (Fa/Fa) and obese Zucker rats was determined using push-pull perfusion. The gavage of a 10.3-kcal (6 ml) liquid diet during lights off was followed by increased CCK release in lean rats (from 13.6 ± 1.1 to 22.1 ± 1.4 fmol in the 1st postprandial period and 18.4 ± 2.5 fmol in the 2nd postprandial period). An identical meal load resulted in no postprandial increase in CCK release in obese rats, despite the fact that high-K+ artificial cerebrospinal fluid evoked CCK outflow in all animals. Intubation of 6 ml of nonnutritive 1% carboxymethylcellulose had no effect. These results are consistent with the suggestion that hypothalamic CCK plays a physiological role in satiety, and they demonstrate that obese Zucker rats have blunted hypothalamic CCK release in response to dietary cues.
hypothalamus; push-pull perfusion; feeding; obesity
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