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Comparison of the effects of intracerebroventricular administration of glucagon-like peptides 1 and 2 on hypothalamic appetite regulating factors and sleep-like behavior in chicks

Kewan, Ahmed Shimatani, Tomohiko Saneyasu, Takaoki Kamisoyama, Hiroshi Honda, Kazuhisa 神戸大学

2022.01.18

概要

Glucagon-like peptide (GLP)-1 and GLP-2, proglucagon-derived brain-gut peptides, function as anorexigenic neuropeptides in mammals. We previously showed that central administration of GLP-1 and GLP-2 potently suppressed food intake in chicks. GLP-1 and GLP-2 specifically activate their receptors GLP-1 receptor (GLP1R) and GLP-2 receptor (GLP2R), respectively in chickens. In adult chickens, GLP1R and GLP2R are expressed in different brain regions. These findings raise the hypothesis that both GLP-1 and GLP-2 function as anorexigenic peptides in the chicken brain but the mechanisms underlying the anorexigenic effects are different between them. In the present study, we compared several aspects of GLP-1 and GLP-2 in chicks. GLP1R mRNA levels in the brain stem and optic lobes were significantly higher than in other parts of the brain, whereas GLP2R mRNA was densely expressed in the telencephalon. Intracerebroventricular administration of either GLP-1 or GLP-2 significantly reduced the mRNA levels of corticotrophin releasing factor and AMP-kinase (AMPK) α1. The mRNA level of proopiomelanocortin was significantly increased, and those of AMPKα2 and GLP2R were significantly decreased by GLP-2, whereas the mRNA level of pyruvate dehydrogenase kinase 4 was significantly increased, and that of GLP1R was significantly decreased by GLP-1. Intracerebroventricular administration of either GLP-1 or GLP-2 induced sleep-like behavior in chicks. Our findings suggest that the anorexigenic peptides GLP-1 and GLP-2 induce similar behavioral changes in chicks, but the mechanism may differ between them.

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Figure captions

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Fig. 1. Distribution of GLP-1 receptor, GLP-2 receptor, and proglucagon mRNAs in the chick brain. Data

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represent means ± SEM of four birds. Groups with different letters are significantly different (P < 0.05).

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Fig. 2.

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appetite-regulating factors in chicks. NPY, neuropeptide Y; POMC, proopiomelanocortin; AgRP, agouti-

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related protein; CRF, corticotrophin releasing factor; AMPKα1, AMP-activated protein kinase alpha 1;

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Effects of central administration of GLP-1 and GLP-2 on the mRNA levels of hypothalamic

AMPKα2, AMP-activated protein kinase alpha 2; PDK4, pyruvate dehydrogenase kinase; GLP1R, glucagon-

like peptide-1 receptor; GLP2R, glucagon-like peptide-2 receptor. Data are the means ± S.E.M. of eight birds

in each group and are expressed as a percentage of the mean in the control group. * Significant with respect

to the control group (P < 0.05).

Fig. 3. Central administration of GLP-1 and GLP-2 on chick posture. Numbers of chicks were as follows:

saline, 12; GLP-1, 11; GLP-2, 12. *Significance with respect to the control group (P < 0.05). (1) active

wakefulness, (2) standing/sitting with eyes open, (3) standing motionless with eyes closed, (4) sitting

motionless with head drooped.

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Fig. 1

Fig. 2

Fig. 3

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