Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, United States.
Behav Brain Res. 2011 Aug 1;221(1):216-26. doi: 10.1016/j.bbr.2011.02.034. Epub 2011 Mar 3.
The effects of ghrelin and obestatin regulation of food intake are different in mammals and chickens. We investigated central effects of ghrelin and obestatin in lines of chickens selected 50 generations for high (HWS) or low (LWS) body weight. We hypothesized that the effect of ghrelin and obestatin on food intake in 5-day-old chicks is mediated by the AMP-activated protein kinase (AMPK) system and selection for body weight alters the brain's response to ghrelin and obestatin by changing the neuronal AMPK system. Although intracerebroventricular (ICV) ghrelin injection decreased food intake in both lines, the threshold for the anorexigenic effect of central ghrelin was lower in LWS than HWS chicks. Obestatin caused a linear dose-dependent increase in food intake in HWS but not LWS chicks. ICV injection of 0.4 nmol ghrelin inhibited hypothalamic AMPK related gene expression and phosphorylation of AMPK α and acetyl-CoA carboxylase (ACC) with the magnitude of inhibition different in the two lines. In contrast, ICV injection of 4 nmol obestatin did not affect mRNA expression of AMPK system or phosphorylation of AMPK and ACC in either line. These data support the premise of a lower threshold for anorexigenic effect of central ghrelin in LWS than HWS chicks, and this difference may be associated with differential hypothalamic AMPK signaling. Additionally, the hypothalamic mRNA level of ghrelin was significantly higher in LWS than HWS, which may have also contributed to the different threshold response to ghrelin in these two lines. The expression of the ghrelin receptor was also higher in the LWS line, but not until 56 days of age. In summary, selection for body weight has resulted in differences in the central ghrelin and obestatin system, and an altered brain AMPK system may contribute to the different neuronal response to ghrelin, but not obestatin.
胃饥饿素和肥胖抑制素对摄食的影响在哺乳动物和鸡中不同。我们研究了选择 50 代高体重（HWS）或低体重（LWS）的鸡的生长激素释放肽和肥胖抑制素的中枢作用。我们假设，5 日龄雏鸡中生长激素释放肽和肥胖抑制素对食物摄入的影响是由 AMP 激活蛋白激酶（AMPK）系统介导的，而体重选择通过改变神经元 AMPK 系统改变了大脑对胃饥饿素和肥胖抑制素的反应。尽管脑室内（ICV）注射胃饥饿素降低了两条鸡线的采食量，但 LWS 雏鸡中中枢胃饥饿素的厌食作用阈值低于 HWS 雏鸡。肥胖抑制素引起 HWS 雏鸡而不是 LWS 雏鸡的线性剂量依赖性食物摄入量增加。ICV 注射 0.4 nmol 胃饥饿素抑制下丘脑 AMPK 相关基因表达和 AMPKα和乙酰辅酶 A 羧化酶（ACC）的磷酸化，两条鸡线的抑制程度不同。相比之下，ICV 注射 4 nmol 肥胖抑制素不会影响 AMPK 系统的 mRNA 表达或两条鸡线中 AMPK 和 ACC 的磷酸化。这些数据支持了 LWS 雏鸡中中枢胃饥饿素的厌食作用阈值低于 HWS 雏鸡的前提，这种差异可能与下丘脑 AMPK 信号传导的差异有关。此外，LWS 鸡的下丘脑胃饥饿素 mRNA 水平显著高于 HWS 鸡，这也可能导致这两条鸡线对胃饥饿素的阈值反应不同。胃饥饿素受体的表达也在 LWS 鸡中更高，但直到 56 天龄时才更高。总之，体重选择导致了中枢胃饥饿素和肥胖抑制素系统的差异，并且改变的大脑 AMPK 系统可能有助于不同的神经元对胃饥饿素的反应，但不是肥胖抑制素。
