Christie Stewart, O'Rielly Rebecca, Li Hui, Wittert Gary A, Page Amanda J
Vagal Afferent Research Group, Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
Vagal Afferent Research Group, Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; Nutrition, Diabetes & Gut Health, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA 5000, Australia.
Peptides. 2020 Sep;131:170371. doi: 10.1016/j.peptides.2020.170371. Epub 2020 Jul 10.
Ghrelin and anandamide (AEA) can regulate the sensitivity of gastric vagal afferents to stretch, an effect mediated via the transient receptor potential vanilloid 1 (TPRV1) channel. High fat diet (HFD)-induced obesity alters the modulatory effects of ghrelin and AEA on gastric vagal afferent sensitivity. This may be a result of altered gastric levels of these hormones and subsequent changes in the expression of their receptors. Therefore, the current study aimed to determine the effects of ghrelin and AEA on vagal afferent cell body mRNA content of cannabinoid 1 receptor (CB1), ghrelin receptor (GHSR), TRPV1, and the enzyme responsible for the breakdown of AEA, fatty acid amide hydrolase (FAAH).
Mice were fed a standard laboratory diet (SLD) or HFD for 12wks. Nodose ganglia were removed and cultured for 14 h in the absence or presence of ghrelin or methAEA (mAEA; stable analogue of AEA). Relative mRNA content of CB1, GHSR, TRPV1, and FAAH were measured.
In nodose cells from SLD-mice, mAEA increased TRPV1 and FAAH mRNA content, and decreased CB1 and GHSR mRNA content. Ghrelin decreased TRPV1, CB1, and GHSR mRNA content. In nodose cells from HFD-mice, mAEA had no effect on TRPV1 mRNA content, and increased CB1, GHSR, and FAAH mRNA content. Ghrelin decreased TRPV1 mRNA content and increased CB1 and GHSR mRNA content.
AEA and ghrelin modulate receptors and breakdown enzymes involved in the mAEA-vagal afferent satiety signalling pathways. This was disrupted in HFD-mice, which may contribute to the altered vagal afferent signalling in obesity.
胃饥饿素和花生四烯乙醇胺（AEA）可调节胃迷走传入神经对牵张的敏感性，该效应通过瞬时受体电位香草酸受体1（TRPV1）通道介导。高脂饮食（HFD）诱导的肥胖会改变胃饥饿素和AEA对胃迷走传入神经敏感性的调节作用。这可能是这些激素的胃内水平改变以及随后其受体表达变化的结果。因此，本研究旨在确定胃饥饿素和AEA对迷走传入神经细胞体中大麻素1受体（CB1）、胃饥饿素受体（GHSR）、TRPV1以及负责AEA分解的酶脂肪酸酰胺水解酶（FAAH）的mRNA含量的影响。
将小鼠喂食标准实验室饮食（SLD）或HFD 12周。取出结状神经节并在不存在或存在胃饥饿素或甲基花生四烯乙醇胺（mAEA；AEA的稳定类似物）的情况下培养14小时。测量CB1、GHSR、TRPV1和FAAH的相对mRNA含量。
在SLD小鼠的结状细胞中，mAEA增加了TRPV1和FAAH的mRNA含量，并降低了CB1和GHSR的mRNA含量。胃饥饿素降低了TRPV1、CB1和GHSR的mRNA含量。在HFD小鼠的结状细胞中，mAEA对TRPV1 mRNA含量没有影响，并增加了CB1、GHSR和FAAH的mRNA含量。胃饥饿素降低了TRPV1 mRNA含量并增加了CB1和GHSR的mRNA含量。
AEA和胃饥饿素调节参与mAEA - 迷走传入神经饱腹感信号通路的受体和分解酶。在HFD小鼠中这种调节被破坏，这可能导致肥胖中迷走传入神经信号的改变。
