Melanin-concentrating hormone regulates leptin synthesis and secretion in rat adipocytes
Melanin-concentrating hormone regulates leptin synthesis and secretion in rat adipocytes
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DOI：
10.2337/diabetes.49.7.1073
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发表时间：
2000-07-01
期刊：
影响因子：
7.7
通讯作者：
Cheatham, B
中科院分区：
文献类型：
--
作者：
Bradley, RL;Kokkotou, EG;Cheatham, B
肥胖是西方社会的一个普遍问题，并与显著的发病率和死亡率相关。能量平衡是由一个复杂的系统调节的，该系统涉及外周信号如瘦素和许多促食欲和厌食神经肽。肥胖症可能是由外周和/或中枢信号的失调引起的。黑色素浓集激素（MCH）是一种下丘脑肽，主要通过中枢神经系统中未表征的信号通路调节摄食行为。瘦素在脂肪组织中表达，通过几种下丘脑神经肽介导其某些作用，特别是刺鼠相关肽、阿黑皮素原和神经肽Y。瘦素的表达受饮食状况、胰岛素和糖皮质激素的调节。此外，某些神经肽可作用于脂肪细胞。然而，尚未研究MCH的潜在影响。我们报告，MCH刺激瘦素mRNA的表达和瘦素分泌。MCH刺激了2倍的增加瘦素分泌的分离大鼠脂肪细胞4小时后的治疗。在分泌的瘦素增加之前，ob mRNA水平迅速和短暂增加; MCH刺激ob mRNA在治疗1小时内增加2.5倍，随后在4小时内下降至基础水平。此外，我们证明了MCH受体SLC-1在脂肪细胞中表达，表明脂肪细胞可能是MCH或MCH样肽在生理条件下的靶点。最后，使用放射免疫分析法，MCH/MCH样肽检测大鼠血浆中。本研究建立了一个新的体外哺乳动物系统，检查MCH信号通路。
Obesity is a common problem in Western society and is associated with significant morbidity and mortality. Energy homeostasis is regulated by a complex system involving both peripheral signals such as leptin and a number of orexigenic and anorectic neuropeptides. Obesity can result from dysregulation of the peripheral and/or central signals. Melanin-concentrating hormone (MCH) is a hypothalamic peptide that is important in the regulation of feeding behavior, primarily via uncharacterized signaling pathways in the central nervous system. Leptin, expressed in adipose tissue, mediates some of its actions through several hypothalamic neuropeptides, notably agouti-related peptide, proopiomelanocortin, and neuropeptide Y. Expression of leptin is regulated by dietary status, insulin, and glucocorticoids. Furthermore, certain neuropeptides may act on adipocytes. However, the potential effect of MCH has not been investigated. We report that MCH stimulates leptin mRNA expression and leptin secretion. MCH stimulated a 2-fold increase in leptin secretion by isolated rat adipocytes after 4 h of treatment. This increase in secreted leptin was preceded by a rapid and transient increase in ob mRNA levels; MCH stimulated a 2.5-fold increase in ob mRNA within 1 h of treatment, followed by a decline to basal levels within 4 h. In addition, we demonstrate that the MCH receptor SLC-1 is expressed in adipocytes, suggesting that fat cells may be targets of MCH or an MCH-like peptide under physiological conditions. Finally, using a radioimmunoassay, MCH/MCH-like peptide was detected in rat plasma. This study establishes a novel in vitro mammalian system for examining MCH signaling pathways.