Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, China.
J Cell Mol Med. 2020 Apr;24(8):4524-4532. doi: 10.1111/jcmm.15110. Epub 2020 Mar 15.
Leptin is well acknowledged as an anorexigenic hormone that plays an important role in feeding control. Hypothalamic GABA system plays a significant role in leptin regulation on feeding and metabolism control. However, the pharmacological relationship of leptin and GABA receptor is still obscure. Therefore, we investigated the effect of leptin or combined with baclofen on the food intake in fasted mice. We detected the changes in hypothalamic c-Fos expression, hypothalamic TH, POMC and GAD67 expression, plasma insulin, POMC and GABA levels to demonstrate the mechanisms. We found that leptin inhibit fasting-induced increased food intake and activated hypothalamic neurons. The inhibitory effect on food intake induced by leptin in fasted mice can be reversed by pretreatment with baclofen. Baclofen reversed leptin's inhibition on c-Fos expression of PAMM in fasted mice. Therefore, these results indicate that leptin might inhibit fasting-triggered activation of PVN neurons via presynaptic GABA synaptic functions which might be partially blocked by pharmacological activating GABA-B. Our findings identify the role of leptin in the regulation of food intake.
瘦素作为一种厌食激素，在摄食控制中起着重要作用，这一点已得到广泛认可。下丘脑 GABA 系统在瘦素调节摄食和代谢控制中起着重要作用。然而，瘦素和 GABA 受体的药理学关系仍不清楚。因此，我们研究了瘦素或联合巴氯芬对禁食小鼠摄食的影响。我们检测了下丘脑 c-Fos 表达、下丘脑 TH、POMC 和 GAD67 表达、血浆胰岛素、POMC 和 GABA 水平的变化，以阐明其机制。结果发现，瘦素抑制了饥饿引起的摄食增加，并激活了下丘脑神经元。巴氯芬预处理可逆转瘦素对禁食小鼠摄食的抑制作用。巴氯芬逆转了瘦素对禁食小鼠 PAMM 中 c-Fos 表达的抑制作用。因此，这些结果表明，瘦素可能通过 GABA 突触前功能抑制饥饿引起的 PVN 神经元的激活，而这种作用可能部分被 GABA-B 的药理学激活所阻断。我们的研究结果确定了瘦素在调节摄食中的作用。
