Endogenous Calcitonin Gene-Related Peptide Regulates Lipid Metabolism and Energy Homeostasis in Male Mice
Endogenous Calcitonin Gene-Related Peptide Regulates Lipid Metabolism and Energy Homeostasis in Male Mice
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内源性降钙素基因相关肽调节雄性小鼠的脂质代谢和能量稳态
DOI：
10.1210/en.2016-1510
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发表时间：
2017-05-01
期刊：
影响因子：
4.8
通讯作者：
Shindo, Takayuki
中科院分区：
文献类型：
--
作者：
Liu, Tian;Kamiyoshi, Akiko;Shindo, Takayuki
降钙素基因相关肽（CGRP）是降钙素/CGRP基因的初级转录物通过选择性剪接产生的生物活性肽。CGRP主要分布在心血管和神经系统中，在那里它充当调节因子。CGRP还在参与代谢调节的器官和组织中表达，包括白色脂肪组织（WAT），其中其功能在很大程度上是未知的。在这项研究中，我们研究了内源性CGRP对代谢功能的影响。当我们给CGRP特异性敲除（CGRP-/-）和野生型（WT）小鼠喂食高脂饮食10周时，我们观察到两组之间的食物摄入量没有差异，但CGRP-/-小鼠的体重和内脏脂肪重量显著降低。CGRP-/-小鼠的脂肪肝变化不太严重，也显示出较低的血清胰岛素和瘦素水平。CGRP-/-小鼠的葡萄糖耐量和胰岛素敏感性优于WT小鼠，呼气分析显示CGRP-/-小鼠的耗氧量更大。CGRP-/-小鼠的脂肪细胞肥大受到抑制，而β-3-肾上腺素能受体、脂联素和脂联素的表达增强。CGRP-/-小鼠中异丙肾上腺素诱导的WAT甘油释放高于WT小鼠，CGRP-/-小鼠显示交感神经活性升高。β受体阻断剂可消除CGRP缺失对肥胖的有益作用。这些结果表明，除了其在心血管系统中的作用外，内源性CGRP是体内代谢和能量稳态的关键调节剂。
Calcitonin gene-related peptide (CGRP) is a bioactive peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is largely distributed in the cardiovascular and nervous systems, where it acts as a regulatory factor. CGRP is also expressed in organs and tissues involved in metabolic regulation, including white adipose tissue (WAT), where its function is largely unknown. In this study, we examined the effects of endogenous CGRP on metabolic function. When we administered a high-fat diet to CGRP-specific knockout (CGRP-/-) and wild-type (WT) mice for 10 weeks, we observed that food intake did not differ between the two groups, but body weight and visceral fat weight were significantly lower in CGRP-/- mice. Fatty liver changes were less severe in CGRP-/- mice, which also showed lower serum insulin and leptin levels. Glucose tolerance and insulin sensitivity were better in CGRP-/- than WT mice, and expired gas analysis revealed greater oxygen consumption by CGRP-/- mice. Adipocyte hypertrophy was suppressed in CGRP-/- mice, while expression of β-3-adrenergic receptor, hormone-sensitive lipase and adiponectin was enhanced. Isoproterenol-induced glycerol release from WAT was higher in CGRP-/- than WT mice, and CGRP-/- mice showed elevated sympathetic nervous activity. β-receptor-blockade canceled the beneficial effects of CGRP deletion on obesity. These results suggest that, in addition to its actions in the cardiovascular system, endogenous CGRP is a key regulator of metabolism and energy homeostasis in vivo.