Olfactory sensory neuron-specific IGF1R knockout in mice results in increased smell perception, insulin resistance and adiposity

Olfaction is fundamental for survival but there is little known about the connection between smell perception and metabolism. In this study we implemented IGF1R knockout mice in the olfactory sensory neurons, by olfactory marker protetin (OMP) Cre specific recombination, and investigated metabolic parameters, smell perception and transcriptome sequencing. We could demonstrate that IGF1R knockout in the olfactory sensory neurons results in enhanced smell perception, insulin resistance under normal chow diet conditions and increased adiposity in mice fed control diet. Transcriptome analysis of the olfactory epithelium revealed differential expression of markers for mature and immature olfactory sensory neurons, being down-regulated and up- regulated respectively, pointing to differentiation-dependent changes that result in increased olfactory perception. Collectively, this study provides evidence that enhanced smell perception can result in insulin resistance and increased adiposity. mRNA profiles of olfactory sensory neurons (OSN) extracted from homozygous tissue-specific IGF1R knockout (OMPIGF1R) and respective control mice (OMPflfl) were generated by deep sequencing, in four replicates using Illumina sequencing嗅觉（Olfaction）是生物体维持生存的核心感知能力，但目前学界对嗅觉感知与代谢之间的关联机制仍知之甚少。本研究通过嗅觉标记蛋白（Olfactory Marker Protein, OMP）介导的特异性Cre重组，在嗅觉感觉神经元（olfactory sensory neurons, OSN）中构建了胰岛素样生长因子1受体（Insulin-like Growth Factor 1 Receptor, IGF1R）敲除小鼠模型，并对代谢参数、嗅觉感知能力及转录组测序结果开展了系统性分析。研究结果显示，嗅觉感觉神经元中的IGF1R敲除可提升小鼠的嗅觉感知能力，在普通饲料饲养条件下诱发胰岛素抵抗，且使饲喂对照饲料的小鼠体脂含量升高。对嗅觉上皮组织的转录组分析表明，成熟与未成熟嗅觉感觉神经元的标志物呈现差异化表达：成熟神经元标志物表达下调，未成熟神经元标志物表达上调，提示嗅觉感知能力的提升源于与神经元分化相关的改变。综上，本研究证实增强的嗅觉感知可诱发胰岛素抵抗与体脂含量升高。本研究采用Illumina测序平台开展深度测序，通过4次生物学重复，对提取自纯合组织特异性IGF1R敲除（OMPIGF1R）小鼠及其对照（OMPflfl）的嗅觉感觉神经元的mRNA表达谱进行了检测。