National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA.
National Institute of Nursing Research, Bethesda, MD 20892, USA.
Int J Mol Sci. 2024 Aug 28;25(17):9330. doi: 10.3390/ijms25179330.
The incidence of obesity has markedly increased globally over the last several decades and is believed to be associated with the easier availability of energy-dense foods, including high-fat foods. The reinforcing hedonic properties of high-fat foods, including olfactory cues, activate reward centers in the brain, motivating eating behavior. Thus, there is a growing interest in the understanding of the genetic changes that occur in the brain that are associated with obesity and eating behavior. This growing interest has paralleled advances in genomic methods that enable transcriptomic-wide analyses. Here, we examined the transcriptomic-level differences in the olfactory bulb and striatum, regions of the brain associated with olfaction and hedonic food-seeking, respectively, in high-fat-diet (HFD)-fed obese mice. To isolate the dietary effects from obesity, we also examined transcriptomic changes in normal-chow-fed and limited-HFD-fed groups, with the latter being pair-fed with an HFD isocaloric to the consumption of the normal-chow-fed mice. Using RNA sequencing, we identified 274 differentially expressed genes (DEGs) in the striatum and 11 in the olfactory bulb of ad libitum HFD-fed mice compared to the chow-fed group, and thirty-eight DEGs in the striatum between the ad libitum HFD and limited-HFD-fed groups. The DEGs in both tissues were associated with inflammation and immune-related pathways, including oxidative stress and immune function, and with mitochondrial dysfunction and reward pathways in the striatum. These results shed light on potential obesity-associated genes in these regions of the brain.
在过去几十年中，肥胖的发病率在全球范围内显著增加，人们认为这与能量密集型食物（包括高脂肪食物）更容易获得有关。高脂肪食物的强化享乐属性，包括嗅觉线索，激活大脑中的奖励中心，激发进食行为。因此，人们越来越感兴趣的是了解与肥胖和进食行为相关的大脑中发生的遗传变化。这种日益增长的兴趣与基因组学方法的进步平行，这些方法使转录组范围的分析成为可能。在这里，我们研究了高脂肪饮食（HFD）喂养的肥胖小鼠的嗅球和纹状体（分别与嗅觉和享乐性食物寻求相关的大脑区域）的转录组水平差异。为了将饮食影响与肥胖分开，我们还研究了正常饮食喂养和限制 HFD 喂养组的转录组变化，后者与正常饮食喂养的小鼠的 HFD 摄入量等热量配对喂养。使用 RNA 测序，我们在自由进食 HFD 喂养的小鼠的纹状体中鉴定出 274 个差异表达基因（DEG），在嗅球中鉴定出 11 个，在自由进食 HFD 和限制 HFD 喂养组的纹状体中鉴定出 38 个 DEG。这两种组织中的 DEG 都与炎症和免疫相关途径有关，包括氧化应激和免疫功能，以及纹状体中的线粒体功能障碍和奖励途径。这些结果揭示了这些大脑区域中与肥胖相关的潜在基因。
