College of Agronomy, Inner Mongolia Agricultural University, Hohhot, China.
College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, China.
Diabetes Metab Res Rev. 2019 Jul;35(5):e3149. doi: 10.1002/dmrr.3149. Epub 2019 Mar 28.
Amylin, a pancreatic hormone cosecreted with insulin, exerts important anorexic and weight-loss effects. Melanocortin 4 receptor (MC4R) signalling plays a critical role in energy homeostasis; however, its role on amylin-dependent regulation of food intake and adaptive thermogenesis of interscapular brown adipose tissue (IBAT) are unclear. In this study, we examined the effects of amylin on food intake and thermogenesis on IBAT via the MC4R pathway in mice.
Acute food consumption and thermogenesis in IBAT were measured in male wild-type (WT) and MC4R-deficient mice following intraperitoneal injection of amylin and SHU9119, an MC3R/4R antagonist, to determine the role of the central melanocortin system on the hypothalamus and IBAT.
Amylin (50 μg/kg) suppressed feeding and stimulated thermogenesis on IBAT via activation of the MC4R system in mice. Pharmacological blockade of MC4R using SHU9119 (50 μg/kg) attenuated amylin-induced inhibition of feeding and stimulation of thermogenesis in IBAT. No changes were observed when SHU9119 was injected alone. Moreover, amylin significantly increased MC4R expression and c-Fos neuronal signals in the arcuate nucleus and significantly increased acetyl-CoA carboxylase (ACC) phosphorylation in the hypothalamus and IBAT and uncoupling protein-1 (UCP1) expression in the IBAT of WT mice via the MC4R pathway.
The melanocortin system was involved in amylin-induced suppression of food intake and activation of thermogenesis in both the hypothalamus and IBAT via modulation of ACC phosphorylation and UCP1 expression.
胰淀素是一种与胰岛素共分泌的胰腺激素，具有重要的厌食和减肥作用。黑皮质素 4 受体（MC4R）信号在能量平衡中发挥着关键作用；然而，其在胰淀素依赖性调节食物摄入和肩胛间棕色脂肪组织（IBAT）适应性产热中的作用尚不清楚。在这项研究中，我们通过 MC4R 通路在小鼠中研究了胰淀素对食物摄入和 IBAT 产热的影响。
雄性野生型（WT）和 MC4R 缺陷型小鼠经腹腔注射胰淀素和 SHU9119（一种 MC3R/4R 拮抗剂）后，测量急性食物消耗和 IBAT 产热，以确定中枢黑皮质素系统对下丘脑和 IBAT 的作用。
胰淀素（50μg/kg）通过激活 MC4R 系统抑制小鼠进食并刺激 IBAT 产热。用 SHU9119（50μg/kg）药理学阻断 MC4R 可减弱胰淀素诱导的进食抑制和 IBAT 产热刺激。单独注射 SHU9119 时未观察到变化。此外，胰淀素通过 MC4R 通路显著增加 WT 小鼠弓状核中的 MC4R 表达和 c-Fos 神经元信号，显著增加下丘脑和 IBAT 中的乙酰辅酶 A 羧化酶（ACC）磷酸化以及 IBAT 中的解偶联蛋白 1（UCP1）表达。
黑皮质素系统通过调节 ACC 磷酸化和 UCP1 表达，参与了胰淀素诱导的食物摄入抑制和下丘脑和 IBAT 产热激活。
