Institute for Translational Medicine, Medical School, University of Pécs, 12 Szigeti street, Pécs, 7624, Hungary.
Research Group for Mood Disorders, Centre for Neuroscience, Medical School, University of Pécs, Pécs, Hungary.
Sci Rep. 2024 Sep 30;14(1):22676. doi: 10.1038/s41598-024-73825-7.
Middle-aged obesity and aging anorexia with muscle loss (sarcopenia) of old people present public health burden. These alterations may appear both in humans and rodents suggesting the role for regulatory alterations. Previously, we demonstrated that biphasic changes in the weight-reducing (catabolic) effects of neuropeptides of the hypothalamus-adipose tissue axis (e.g. leptin) may contribute to both trends. With regard to the anabolic effects of the hypothalamic neuropeptide Y (NPY) inhibited by leptin, we hypothesized non-linear age-related changes with shifts in the opposite directions. We investigated the orexigenic and hypometabolic effects of intracerebroventricularly administered NPY (hyperphagia induced by NPY injection or changes in food intake, body weight, heart rate, body temperature, locomotor activity during a 7-day NPY infusion), the immunoreactivity and gene expression of NPY in the hypothalamic arcuate nucleus of male Wistar rats of five age groups from young to old. The orexigenic/hypometabolic efficacy and the immunoreactivity of NPY increased in middle-aged animals preceding the peak of adiposity observed in aging rats, then decreased preceding anorexia and weight loss in old rats. These shifts may contribute to the development of both age-related obesity and aging anorexia, sarcopenia, and should be considered in future drug development targeting the NPY system.
中年肥胖和老年人肌肉减少（肌少症）伴厌食症给公共健康带来了负担。这些变化在人类和啮齿动物中都可能出现，提示存在调节变化的可能性。先前，我们证明了下丘脑-脂肪组织轴神经肽的减肥（分解代谢）作用的双相变化（例如瘦素）可能与这两种趋势都有关。关于瘦素抑制的下丘脑神经肽 Y（NPY）的合成代谢作用，我们假设存在非线性与相反方向转变的年龄相关变化。我们研究了脑室给予 NPY 的食欲刺激和代谢抑制作用（通过 NPY 注射诱导的暴食或食物摄入量、体重、心率、体温、7 天 NPY 输注期间的运动活动的变化）、下丘脑弓状核中 NPY 的免疫反应性和基因表达，雄性 Wistar 大鼠五个年龄组从年轻到老年。在肥胖高峰期之前，中年动物的食欲刺激/代谢抑制作用和 NPY 的免疫反应性增加，然后在老年大鼠出现厌食和体重减轻之前减少。这些转变可能有助于肥胖和厌食症、肌少症的发展，应在未来针对 NPY 系统的药物开发中加以考虑。
