Nerve Gut Research Laboratory, Department of Medicine, University of Adelaide, Frome Road, Adelaide, SA 5005, Australia.
Peptides. 2013 Aug;46:150-8. doi: 10.1016/j.peptides.2013.06.004. Epub 2013 Jun 20.
Leptin, ghrelin and neuropeptide W (NPW) modulate vagal afferent activity, which may underlie their appetite regulatory actions. High fat diet (HFD)-induced obesity induces changes in the plasma levels of these peptides and alters the expression of receptors on vagal afferents. We investigated homologous and heterologous receptor regulation by leptin, ghrelin and NPW. Mice were fed (12 weeks) a standard laboratory diet (SLD) or HFD. Nodose ganglia were cultured overnight in the presence or absence of each peptide. Leptin (LepR), ghrelin (GHS-R), NPW (GPR7) and cholecystokinin type-1 (CCK1R) receptor mRNA, and the plasma leptin, ghrelin and NPW levels were measured. SLD: leptin reduced LepR, GPR7, increased GHS-R and CCK1R mRNA; ghrelin increased LepR, GPR7, CCK1R, and decreased GHS-R. HFD: leptin decreased GHS-R and GPR7, ghrelin increased GHS-R and GPR7. NPW decreased all receptors except GPR7 which increased with HFD. Plasma leptin was higher and NPW lower in HFD. Thus, HFD-induced obesity disrupts inter-regulation of appetite regulatory receptors in vagal afferents.
瘦素、胃饥饿素和神经肽 W（NPW）调节迷走传入活动，这可能是它们调节食欲的作用基础。高脂肪饮食（HFD）诱导的肥胖会改变这些肽的血浆水平，并改变迷走传入纤维上受体的表达。我们研究了瘦素、胃饥饿素和 NPW 对同源和异源受体的调节作用。用标准实验室饮食（SLD）或 HFD 喂养小鼠 12 周。在存在或不存在每种肽的情况下，将迷走神经节培养过夜。测量瘦素（LepR）、胃饥饿素（GHS-R）、NPW（GPR7）和胆囊收缩素-1 型（CCK1R）受体 mRNA 以及血浆瘦素、胃饥饿素和 NPW 水平。SLD：瘦素降低 LepR、GPR7，增加 GHS-R 和 CCK1R mRNA；胃饥饿素增加 LepR、GPR7、CCK1R，并降低 GHS-R。HFD：瘦素降低 GHS-R 和 GPR7，胃饥饿素增加 GHS-R 和 GPR7。NPW 除 GPR7 外降低所有受体，而 GPR7 在 HFD 下增加。HFD 中血浆瘦素水平升高，NPW 水平降低。因此，HFD 诱导的肥胖会破坏迷走传入纤维中食欲调节受体的相互调节。
