当前位置：
X-MOL 学术
›
ACS Appl. Energy Mater.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Calcitonin-Receptor-Like Receptor Signaling Governs Intestinal Lymphatic Innervation and Lipid Uptake
ACS Applied Energy Materials ( IF 5.4 ) Pub Date : 2019-01-29 00:00:00 , DOI: 10.1021/acsptsci.8b00061 Reema B. Davis 1 , Shengli Ding 1 , Natalie R. Nielsen 1 , John B. Pawlak 1 , Elizabeth S. Blakeney 1 , Kathleen M. Caron 1
ACS Applied Energy Materials ( IF 5.4 ) Pub Date : 2019-01-29 00:00:00 , DOI: 10.1021/acsptsci.8b00061 Reema B. Davis 1 , Shengli Ding 1 , Natalie R. Nielsen 1 , John B. Pawlak 1 , Elizabeth S. Blakeney 1 , Kathleen M. Caron 1
Affiliation
|
The absorption of dietary fat requires complex neuroendocrine-mediated regulation of chylomicron trafficking through enterocytes and intestinal lymphatic vessels. Calcitonin-receptor-like receptor (Calcrl) is a G protein-coupled receptor that can bind either a lymphangiogenic ligand adrenomedullin, with coreceptor RAMP2, or the neuropeptide CGRP, with coreceptor RAMP1. The extent to which this common GPCR controls lipid absorption via lymphatics or enteric innervation remains unclear. We used conditional and inducible genetic deletion of Calcrl in lymphatics to elucidate the pathophysiological consequences of this receptor pathway under conditions of high-fat diet. Inefficient absorption of dietary fat coupled with altered lymphatic endothelial junctions in Calcrlfl/fl/Prox1-CreERT2 mice results in excessive, transcellular lipid accumulation and abnormal enterocyte chylomicron processing and failure to gain weight. Interestingly, Calcrlfl/fl/Prox1-CreERT2 animals show reduced and disorganized mucosal and submucosal innervation. Consistently, mice with genetic loss of the CGRP coreceptor RAMP1 also displayed mucosal and submucosal innervation deficits, substantiating the CGRP-biased function of Calcrl in the neurolymphocrine axis. Thus, the common Calcrl receptor is a critical regulator of lipid absorption through its cell-specific functions in neurolymphocrine crosstalk.
中文翻译：
降钙素受体样受体信号控制肠道淋巴神经支配和脂质摄取
膳食脂肪的吸收需要复杂的神经内分泌介导的乳糜微粒通过肠上皮细胞和肠淋巴管运输的调节。降钙素受体样受体（Calcrl）是一种G蛋白偶联受体，可以与具有共受体RAMP2的淋巴管生成配体肾上腺髓质素或具有共受体RAMP1的神经肽CGRP结合。尚不清楚这种常见的GPCR通过淋巴管或肠神经支配控制脂质吸收的程度。我们使用了有条件的和可诱导的Calcrl基因在淋巴管中的基因缺失，以阐明高脂饮食条件下该受体途径的病理生理后果。饮食脂肪吸收不足，伴有Calcrl淋巴管内皮连接改变fl / fl / Prox1-CreER T2小鼠导致过量的跨细胞脂质蓄积和异常的肠上皮细胞乳糜微粒加工以及体重增加。有趣的是， Calcr1f1 / f1 / Prox1-CreER T2动物表现出减少的和无组织的粘膜和粘膜下神经支配。一致地，遗传丢失了CGRP共受体RAMP1的小鼠也表现出粘膜和粘膜下神经支配缺陷，从而证实了Calcr在神经淋巴球轴上的CGRP偏向功能。因此，常见的Calcr受体通过其在神经淋巴结串扰中的细胞特异性功能，是脂质吸收的关键调节剂。
更新日期：2019-01-29
中文翻译：
降钙素受体样受体信号控制肠道淋巴神经支配和脂质摄取
膳食脂肪的吸收需要复杂的神经内分泌介导的乳糜微粒通过肠上皮细胞和肠淋巴管运输的调节。降钙素受体样受体（Calcrl）是一种G蛋白偶联受体，可以与具有共受体RAMP2的淋巴管生成配体肾上腺髓质素或具有共受体RAMP1的神经肽CGRP结合。尚不清楚这种常见的GPCR通过淋巴管或肠神经支配控制脂质吸收的程度。我们使用了有条件的和可诱导的Calcrl基因在淋巴管中的基因缺失，以阐明高脂饮食条件下该受体途径的病理生理后果。饮食脂肪吸收不足，伴有Calcrl淋巴管内皮连接改变fl / fl / Prox1-CreER T2小鼠导致过量的跨细胞脂质蓄积和异常的肠上皮细胞乳糜微粒加工以及体重增加。有趣的是， Calcr1f1 / f1 / Prox1-CreER T2动物表现出减少的和无组织的粘膜和粘膜下神经支配。一致地，遗传丢失了CGRP共受体RAMP1的小鼠也表现出粘膜和粘膜下神经支配缺陷，从而证实了Calcr在神经淋巴球轴上的CGRP偏向功能。因此，常见的Calcr受体通过其在神经淋巴结串扰中的细胞特异性功能，是脂质吸收的关键调节剂。
京公网安备 11010802027423号