Department of Food Science, Central Taiwan University of Science and Technology, Taichung City 406, Taiwan.
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
Horm Behav. 2018 Feb;98:173-182. doi: 10.1016/j.yhbeh.2017.12.019. Epub 2018 Jan 11.
Leptin is an adipose tissue hormone which plays an important role in regulating energy homeostasis. Amphetamine (AMPH) is a drug of appetite suppressant, which exerts its effect by decreasing the expression of hypothalamic neuropeptide Y (NPY) and increasing that of cocaine- and amphetamine-regulated transcript (CART). This study investigated whether leptin, the leptin receptor (LepRb) and the signal transducer and activator of transcription-3 (STAT3) were involved in NPY/CART-mediated appetite suppression in AMPH-treated rats. Rats were given AMPH daily for four days, and changes in the levels of blood leptin and hypothalamic NPY, CART, LepRb, Janus kinases 2 (JAK2), and STAT3 were assessed and compared. During the AMPH treatment, blood leptin levels and hypothalamic NPY expression decreased, with the largest reduction observed on Day 2. By contrast, the expression of hypothalamic CART, LepRb, JAK2, and STAT3 increased, with the maximum response on Day 2. Furthermore, the binding activity of pSTAT3/DNA increased and was expressed in similar pattern to that of CART, LepRb, and JAK2. An intracerebroventricular infusion of NPY antisense 60min prior to AMPH treatment increased the levels of leptin, as well as the expression in LepRb, JAK2, and CART, whereas an infusion of STAT3 antisense decreased these levels and the expression of these parameters. The results suggest that blood leptin and hypothalamic LepRb-JAK2-STAT3 signaling involved in NPY-CART-regulated appetite suppression in AMPH-treated rats. The findings may aid understanding the role of leptin-LepRb during the treatment of anorectic drugs.
瘦素是一种脂肪组织激素，在调节能量平衡中起着重要作用。安非他命（AMPH）是一种食欲抑制剂药物，通过降低下丘脑神经肽 Y（NPY）的表达和增加可卡因和安非他命调节转录物（CART）的表达来发挥作用。本研究探讨了瘦素、瘦素受体（LepRb）和信号转导和转录激活因子 3（STAT3）是否参与 AMPH 处理大鼠中 NPY/CART 介导的食欲抑制。大鼠每天给予 AMPH 治疗 4 天，评估并比较血液瘦素水平和下丘脑 NPY、CART、LepRb、Janus 激酶 2（JAK2）和 STAT3 的变化。在 AMPH 治疗期间，血液瘦素水平和下丘脑 NPY 表达降低，第 2 天观察到最大降低。相比之下，下丘脑 CART、LepRb、JAK2 和 STAT3 的表达增加，第 2 天达到最大反应。此外，pSTAT3/DNA 的结合活性增加，并以与 CART、LepRb 和 JAK2 相似的方式表达。在 AMPH 治疗前 60 分钟向侧脑室输注 NPY 反义寡核苷酸增加了瘦素水平，以及 LepRb、JAK2 和 CART 的表达，而 STAT3 反义寡核苷酸的输注降低了这些水平和这些参数的表达。结果表明，血液瘦素和下丘脑 LepRb-JAK2-STAT3 信号参与了 AMPH 处理大鼠中 NPY/CART 调节的食欲抑制。这些发现可能有助于理解瘦素-LepRb 在厌食症药物治疗中的作用。
