Beck Bernard, Richy Sébastien, Stricker-Krongrad Alain
UHP/EA 3453 - IFR 111-Systèmes Neuromodulateurs des Comportements Ingestifs-38, rue Lionnois 54000 Nancy, France.
Life Sci. 2004 Dec 10;76(4):473-8. doi: 10.1016/j.lfs.2004.09.001.
Ghrelin is a new orexigenic and adipogenic peptide primarily produced by the stomach and the hypothalamus. In the present experiment, we determined the circulating ghrelin levels in 60-week old fa/fa Zucker rats with a well-established obesity (n = 12) and in their lean (FA/FA) counterparts (n = 12). We also tested the feeding response of both groups to intra-peritoneal (I.P.) injection of ghrelin agonist and antagonist. Obese rats ate significantly more than the lean rats (21.7 +/- 1.1 vs. 18.3 +/- 0.3 g/day; p < 0.01). Their plasma ghrelin concentration was 35% higher than that in the lean homozygous rats (p < 0.025). GHRP-6 (1 mg/kg I.P, a GHS-R agonist) stimulated food intake in lean but not in obese rats (p < 0.01), whereas [D-Lys)]-GHRP-6 (12 mg/kg I.P., a GHS-R antagonist) decreased food intake in both groups (p < 0.0001). These results indicate that the obese Zucker rat is characterized by an increase in plasma ghrelin concentrations and by an attenuated response to a GHS-R agonist. They support a role for ghrelin in the development of obesity in the absence of leptin signaling.
胃饥饿素是一种主要由胃和下丘脑产生的新型促食欲和促脂肪生成肽。在本实验中，我们测定了60周龄、已确诊肥胖的fa/fa Zucker大鼠（n = 12）及其瘦型（FA/FA）对照大鼠（n = 12）的循环胃饥饿素水平。我们还测试了两组对腹腔注射胃饥饿素激动剂和拮抗剂的摄食反应。肥胖大鼠的食量显著高于瘦大鼠（21.7±1.1 vs. 18.3±0.3克/天；p < 0.01）。它们的血浆胃饥饿素浓度比瘦型纯合大鼠高35%（p < 0.025）。生长激素释放肽-6（1毫克/千克腹腔注射，一种生长激素促分泌素受体激动剂）刺激瘦大鼠的食物摄入，但不刺激肥胖大鼠（p < 0.01），而[D-赖氨酸]-生长激素释放肽-6（12毫克/千克腹腔注射，一种生长激素促分泌素受体拮抗剂）使两组的食物摄入量均减少（p < 0.0001）。这些结果表明，肥胖的Zucker大鼠的特征是血浆胃饥饿素浓度升高以及对生长激素促分泌素受体激动剂的反应减弱。它们支持胃饥饿素在缺乏瘦素信号的情况下在肥胖发生过程中起作用。
