Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA.
Nutr Neurosci. 2022 May;25(5):1105-1114. doi: 10.1080/1028415X.2020.1840049. Epub 2020 Nov 5.
The orexin peptides promote hedonic intake and other reward behaviors through different brain sites. The opioid dynorphin peptides are co-released with orexin peptides but block their effects on reward in the ventral tegmental area (VTA). We previously showed that in the paraventricular hypothalamic nucleus (PVN), dynorphin and not orexin peptides enhance hedonic intake, suggesting they have brain-site-specific effects. Obesity alters the expression of orexin and dynorphin receptors, but whether their expression across different brain sites is important to hedonic intake is unclear. We hypothesized that hedonic intake is regulated by orexin and dynorphin peptides in PVN and that hedonic intake in obesity correlates with expression of their receptors. Here we show that in mice, injection of DYN-A (an opioid dynorphin peptide) in the PVN enhanced hedonic intake, whereas in the VTA, injection of OXA (orexin-A, an orexin peptide) enhanced hedonic intake. In PVN, OXA blunted the increase in hedonic intake caused by DYN-A. In PVN, injection of norBNI (opioid receptor antagonist) reduced hedonic intake but a subsequent OXA injection failed to increase hedonic intake, suggesting that OXA activity in PVN is not influenced by endogenous opioid activity. In the PVN, DYN-A increased the intake of the less-preferred food in a two-food choice task. In obese mice fed a cafeteria diet, orexin 1 receptor mRNA across brain sites involved in hedonic intake correlated with fat preference but not caloric intake. Together, these data support that orexin and dynorphin peptides regulate hedonic intake in an opposing manner with brain-site-specific effects.
食欲肽促进享乐性摄食和其他奖励行为通过不同的脑区。阿片样肽强啡肽与食欲肽共同释放，但在腹侧被盖区（VTA）阻断其对奖励的作用。我们之前表明，在下丘脑室旁核（PVN），强啡肽而不是食欲肽增强享乐性摄食，表明它们具有脑区特异性作用。肥胖改变了食欲肽和强啡肽受体的表达，但它们在不同脑区的表达是否对享乐性摄食很重要尚不清楚。我们假设，PVN 中的食欲肽和强啡肽肽调节享乐性摄食，而肥胖中的享乐性摄食与它们的受体表达相关。在这里，我们表明，在小鼠中，PVN 中的 DYN-A（一种阿片样强啡肽肽）注射增强了享乐性摄食，而在 VTA 中，OXA（食欲肽-A，一种食欲肽）注射增强了享乐性摄食。在 PVN 中，OXA 减弱了 DYN-A 引起的享乐性摄食增加。在 PVN 中，注射 norBNI（阿片受体拮抗剂）减少了享乐性摄食，但随后的 OXA 注射未能增加享乐性摄食，表明 PVN 中的 OXA 活性不受内源性阿片样物质活性的影响。在 PVN 中，DYN-A 增加了两种食物选择任务中不太受欢迎食物的摄入量。在喂食 cafeteria 饮食的肥胖小鼠中，参与享乐性摄食的脑区的食欲肽 1 受体 mRNA 与脂肪偏好相关，但与热量摄入无关。总之，这些数据支持食欲肽和强啡肽以相反的方式通过脑区特异性作用来调节享乐性摄食。
