Increased receptor sensitivity to neuropeptide Y in the hypothalamus may underlie transient hyperphagia and body weight gain

Jul 4, 1998Regulatory peptides

Higher sensitivity to neuropeptide Y in the hypothalamus may cause temporary overeating and weight gain

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Abstract

Microinjection of 4 micrograms of colchicine in the ventromedial hypothalamus of rats leads to rapid and transient hyperphagia and body weight gain.

COL-injected rats exhibited hyperphagia during both light and dark periods following the treatment.
PreproNPY mRNA levels in the arcuate nucleus and NPY levels in the paraventricular nucleus decreased over time in COL-injected rats.
Food intake in response to NPY injections was significantly higher in COL-injected rats compared to controls.
The latency to initiate feeding was markedly reduced in COL-injected rats after NPY administration.
The enhanced feeding response in COL-injected rats persisted for only 4 days, coinciding with the transient hyperphagia.
Hyperphagia in COL-treated rats was found to be dependent on endogenous NPY, as indicated by the suppressive effects of the NPY Y1 receptor antagonist.

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Disruption of neural signaling by microinjection of a neurotoxin, colchicine (COL), in the ventromedial hypothalamus (VMH) of rats results in rapid and transient hyperphagia and body weight gain. Since neuropeptide Y (NPY) is a potent hypothalamic orexigenic signal and continuous NPY receptor activation by intracerebroventricular (icv) NPY infusion results in hyperphagia and obesity, we tested the hypothesis that altered NPYergic signaling may underlie the transient hyperphagia in COL-injected rats. Immediately following COL (4 microg) microinjections in the ventromedial nucleus (VMN) rats displayed hyperphagia both during the lights-on and lights-off periods. Concomitant with hyperphagia, preproNPY mRNA levels in the arcuate nucleus and NPY levels in the paraventricular nucleus decreased in a time-dependent manner. However, food intake in response to intracerebroventricular injections of NPY (29, 117 and 470 pmole) was significantly higher in COL-injected rats and the latency to initiation of feeding was markedly reduced as compared to controls. The smallest dose of NPY which was virtually ineffective in control rats, evoked near maximal intake in COL-injected rats. This enhanced response lasted for only 4 days paralleling the transient hyperphagia. The NPY Y1 receptor antagonist 1229U91 (5 or 30 microg/rat, icv) significantly suppressed feeding in COL-treated rats thereby indicating that hyperphagia in these rats was dependent upon endogenous NPY. Overall, these studies demonstrate that not only high levels, but low levels of NPY may also result in hyperphagia and increased body weight and this hyperphagia may be attributed to the rapid development of NPY Y1 receptor hypersensitivity.

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Increased receptor sensitivity to neuropeptide Y in the hypothalamus may underlie transient hyperphagia and body weight gain

Abstract

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