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定义脂联素对小鼠胃底平滑肌松弛作用的分子机制:饮食失调管理的潜在转化视角。

Defining the Molecular Mechanisms of the Relaxant Action of Adiponectin on Murine Gastric Fundus Smooth Muscle: Potential Translational Perspectives on Eating Disorder Management.

机构信息

Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, 50134 Florence, Italy.

Department of Health Sciences, Psychiatry Unit, University of Florence, 50134 Firenze, Italy.

出版信息

Int J Mol Sci. 2023 Jan 5;24(2):1082. doi: 10.3390/ijms24021082.

Abstract

Adiponectin (ADPN), a hormone produced by adipose tissue, facilitates gastric relaxation and can be a satiety signal in the network connecting peripheral organs and the central nervous system for feeding behavior control. Here, we performed preclinical research by morpho-functional analyses on murine gastric fundus smooth muscle to add insights into the molecular mechanisms underpinning ADPN action. Moreover, we conducted a clinical study to evaluate the potential use of ADPN as a biomarker for eating disorders (ED) based on the demonstrated gastric alterations and hormone level fluctuations that are often associated with ED. The clinical study recruited patients with ED and healthy controls who underwent blood draws for ADPN dosage and psychopathology evaluation tests. The findings of this basic research support the ADPN relaxant action, as indicated by the smooth muscle cell membrane pro-relaxant effects, with mild modifications of contractile apparatus and slight inhibitory effects on gap junctions. All of these actions engaged the ADPN/nitric oxide/guanylate cyclase pathway. The clinical data failed to unravel a correlation between ADPN levels and the considered ED, thus negating the potential use of ADPN as a valid biomarker for ED management for the moment. Nevertheless, this adipokine can modulate physiological eating behavior, and its effects deserve further investigation.

摘要

脂联素 (ADPN) 是一种由脂肪组织产生的激素,它促进胃的松弛,并且可以作为连接外周器官和中枢神经系统的网络中的饱腹感信号,以控制进食行为。在这里,我们通过对小鼠胃底平滑肌的形态和功能分析进行了临床前研究,以深入了解 ADPN 作用的分子机制。此外,我们进行了一项临床研究,以评估 ADPN 作为进食障碍 (ED) 生物标志物的潜在用途,因为 ED 常伴有胃改变和激素水平波动,这些改变已经得到了证实。该临床研究招募了 ED 患者和健康对照组,他们进行了血液采集,以进行 ADPN 剂量和精神病理学评估测试。这项基础研究的结果支持 ADPN 的松弛作用,这表现为平滑肌细胞膜的促松弛作用,对收缩装置进行了轻微的修饰,并对缝隙连接产生轻微的抑制作用。所有这些作用都涉及 ADPN/一氧化氮/鸟苷酸环化酶途径。临床数据未能揭示 ADPN 水平与所考虑的 ED 之间的相关性,因此目前否定了 ADPN 作为 ED 管理的有效生物标志物的潜在用途。然而,这种脂肪细胞因子可以调节生理进食行为,其作用值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eaa/9867455/c6d7a86b52f3/ijms-24-01082-g001.jpg

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