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Amylin/Calcitonin Receptor-Mediated Signaling in POMC Neurons Influences Energy Balance and Locomotor Activity in Chow-Fed Male Mice
Diabetes ( IF 6.2 ) Pub Date : 2020-03-09 , DOI: 10.2337/db19-0849
Bernd Coester 1 , Christina Koester-Hegmann 1 , Thomas A Lutz 1 , Christelle Le Foll 2
Affiliation  

Amylin, a pancreatic hormone and neuropeptide, acts principally in the hindbrain to decrease food intake and has recently been shown to act as a neurotrophic factor to control the development of area postrema → nucleus of the solitary tract and arcuate hypothalamic nucleus → paraventricular nucleus axonal fiber outgrowth. Amylin is also able to activate ERK signaling specifically in POMC neurons independently of leptin. For investigation of the physiological role of amylin signaling in POMC neurons, the core component of the amylin receptor, calcitonin receptor (CTR), was depleted from POMC neurons using an inducible mouse model. The loss of CTR in POMC neurons leads to increased body weight gain, increased adiposity, and glucose intolerance in male knockout mice, characterized by decreased energy expenditure (EE) and decreased expression of uncoupling protein 1 (UCP1) in brown adipose tissue. Furthermore, a decreased spontaneous locomotor activity and absent thermogenic reaction to the application of the amylin receptor agonist were observed in male and female mice. Together, these results show a significant physiological impact of amylin/calcitonin signaling in CTR-POMC neurons on energy metabolism and demonstrate the need for sex-specific approaches in obesity research and potentially treatment.

中文翻译:

POMC 神经元中胰淀素/降钙素受体介导的信号传导影响饲料喂养的雄性小鼠的能量平衡和运动活动

胰淀素是一种胰腺激素和神经肽,主要作用于后脑以减少食物摄入,最近已被证明作为神经营养因子来控制后区→孤束核和弓状下丘脑核→室旁核轴突纤维的发展生长。Amylin 还能够独立于瘦素在 POMC 神经元中特异性激活 ERK 信号。为了研究胰淀素信号在 POMC 神经元中的生理作用,胰淀素受体的核心成分,降钙素受体 (CTR),使用诱导型小鼠模型从 POMC 神经元中耗尽。POMC 神经元中 CTR 的丧失导致雄性基因敲除小鼠的体重增加增加、肥胖增加和葡萄糖耐受不良,其特征是能量消耗 (EE) 减少和棕色脂肪组织中解偶联蛋白 1 (UCP1) 的表达减少。此外,在雄性和雌性小鼠中观察到自发运动活动减少和缺乏对胰淀素受体激动剂应用的产热反应。总之,这些结果显示了 CTR-POMC 神经元中胰淀素/降钙素信号传导对能量代谢的显着生理影响,并证明了肥胖研究和潜在治疗中需要采用性别特异性方法。
更新日期:2020-03-09
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