Previous studies indicate that hypothalamic prolactin-releasing peptide (PrRP), signaling via GPR10 and neuropeptide FF2 receptor, is involved in energy homeostasis, stress responses, and cardiovascular regulation. Energy homeostasis depends on the balance between food intake regulation and energy expenditure, in which the hypothalamus plays a key role. The lipidization of PrRP31 with palmitoyl acid allows it to produce its anorexigenic effect after repeated peripheral administration and to reduce body weight and improve metabolic parameters in diet-induced obese (DIO) mice. The aim of this study was to reveal the transient and long-lasting changes in neuronal activity via c-Fos and FosB immunohistochemistry in brain nuclei related to food intake regulation and energy homeostasis during the first days of treatment with a newly designed lipidized analog of PrRP31 (palm¹¹-PrRP31) with promising antiobesity effects. The data revealed that the anorexigenic effect of repeated application of palm¹¹-PrRP31 was associated with delayed but gradually significantly reduced cumulative food intake in mice as well as with a significant reduction in their body weight. Moreover, while the repeated application of palm¹¹-PrRP31 was associated with a significant reduction in acute cell activity in the paraventricular hypothalamic nucleus (PVN) and nucleus of the solitary tract (NTS) compare to its acute treatment, both acute and long-lasting cell activity in the dorsomedial hypothalamic nucleus (DMN) were increased. The data indicate that DMN neurons might be tonically activated after repeated administration of lipidized PrRP analogs that may be associated with the process of long-term adaptation to modified energy homeostasis.

先前的研究表明，通过GPR10和神经肽FF2受体发出信号的下丘脑催乳素释放肽（PrRP）参与能量稳态，应激反应和心血管调节。能量稳态取决于食物摄入调节和能量消耗之间的平衡，其中下丘脑起关键作用。棕榈酸对PrRP31的脂化作用使其在反复外周给药后能产生其厌食作用，并能减轻饮食诱导的肥胖（DIO）小鼠的体重并改善其代谢参数。¹¹ -PrRP31）具有良好的抗肥胖作用。数据显示，重复施用棕榈¹¹ -PrRP31的厌食作用与延迟但逐渐显着减少小鼠的累积食物摄入量以及体重的显着降低有关。而且，虽然反复应用手掌¹¹与它的急性治疗相比，-PrRP31与脑室下丘脑下丘脑核（PVN）和孤立道核（NTS）的急性细胞活性显着降低有关，在背体下丘脑丘脑核（DMN）中急性和持久的细胞活性）增加了。数据表明，在重复施用脂化的PrRP类似物后，DMN神经元可能会被声调激活，这可能与长期适应改良的能量稳态的过程有关。