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与小鼠和人类食物成瘾易感性相关的 miRNA 特征。

miRNA signatures associated with vulnerability to food addiction in mice and humans.

机构信息

Laboratory of Neuropharmacology-Neurophar, Department of Medicine and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.

出版信息

J Clin Invest. 2022 May 16;132(10). doi: 10.1172/JCI156281.

DOI:10.1172/JCI156281
PMID:35349487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9106358/
Abstract

Food addiction is characterized by a loss of behavioral control over food intake and is associated with obesity and other eating disorders. The mechanisms underlying this behavioral disorder are largely unknown. We aimed to investigate the changes in miRNA expression promoted by food addiction in animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. We found sharp similitudes between miRNA signatures in the medial prefrontal cortex (mPFC) of our animal cohort and circulating miRNA levels in our human cohort, which allowed us to identify several miRNAs of potential interest in the development of this disorder. Tough decoy (TuD) inhibition of miRNA-29c-3p in the mouse mPFC promoted persistence of the response and enhanced vulnerability to developing food addiction, whereas miRNA-665-3p inhibition promoted compulsion-like behavior and also enhanced food addiction vulnerability. In contrast, we found that miRNA-137-3p inhibition in the mPFC did not lead to the development of food addiction. Therefore, miRNA-29c-3p and miRNA-665-3p could be acting as protective factors with regard to food addiction. We believe the elucidation of these epigenetic mechanisms will lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related disorders based on the strategies now available to modify miRNA activity and expression.

摘要

食物成瘾的特点是对食物摄入量失去行为控制，并且与肥胖和其他饮食失调有关。这种行为障碍的机制在很大程度上尚不清楚。我们旨在研究动物和人类中食物成瘾引起的 miRNA 表达变化及其在该疾病行为特征的机制中的作用。我们发现，我们动物队列的内侧前额叶皮层（mPFC）中的 miRNA 特征与我们人类队列中的循环 miRNA 水平之间存在明显的相似性，这使我们能够鉴定出几种在该疾病发展中具有潜在作用的 miRNA。在小鼠 mPFC 中，坚韧诱饵（TuD）抑制 miRNA-29c-3p 可促进反应的持久性并增强对食物成瘾的易感性，而 miRNA-665-3p 抑制可促进强迫样行为并增强食物成瘾的易感性。相比之下，我们发现 mPFC 中的 miRNA-137-3p 抑制不会导致食物成瘾的发展。因此，miRNA-29c-3p 和 miRNA-665-3p 可能是针对食物成瘾的保护因素。我们相信，阐明这些表观遗传机制将有助于确定创新的生物标志物，并可能为食物成瘾和相关障碍提供未来的干预措施，基于目前可用于修饰 miRNA 活性和表达的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/c03f493c0f21/jci-132-156281-g201.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/151157240c9d/jci-132-156281-g194.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/cffa7bade310/jci-132-156281-g195.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/15b262bd6624/jci-132-156281-g196.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/5feb6201caae/jci-132-156281-g197.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/62148f76ba13/jci-132-156281-g198.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/d01d3f7f6aa0/jci-132-156281-g199.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/434b22b1af13/jci-132-156281-g200.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/c03f493c0f21/jci-132-156281-g201.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/151157240c9d/jci-132-156281-g194.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/cffa7bade310/jci-132-156281-g195.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/15b262bd6624/jci-132-156281-g196.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/5feb6201caae/jci-132-156281-g197.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/62148f76ba13/jci-132-156281-g198.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/d01d3f7f6aa0/jci-132-156281-g199.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/434b22b1af13/jci-132-156281-g200.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e38/9106358/c03f493c0f21/jci-132-156281-g201.jpg

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