Nutrigenomics, Biomarkers and Risk Evaluation (NuBE) Group, University of the Balearic Islands (UIB), 07122 Palma, Spain.
CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Int J Mol Sci. 2023 Dec 22;25(1):228. doi: 10.3390/ijms25010228.
The intake of high-fat diets (HFDs) and obesity are linked to cognitive impairment. Here, we aimed to investigate whether an early metabolically obese, normal-weight (MONW) phenotype, induced with an HFD in young rats, also leads to cognitive dysfunction and to evaluate the potential cognitive benefits of neonatal intake of leptin. To achieve this, Wistar rats orally received physiological doses of leptin or its vehicle during lactation, followed by 11 weeks of pair-feeding with an HFD or control diet post-weaning. Working memory was assessed using a T-maze, and gene expression in the hippocampus and peripheral blood mononuclear cells (PBMCs) was assessed with real-time RT-qPCR to identify cognition biomarkers. Young MONW-like rats showed hippocampal gene expression changes and decreased working memory. Animals receiving leptin during lactation presented similar gene expression changes but preserved working memory despite HFD intake, partly due to improved insulin sensitivity. Notably, PBMC expression appears as an accessible biomarker of cognitive health, reflecting both the detrimental effect of HFD intake at early ages despite the absence of obesity and the positive effects of neonatal leptin treatment on cognition. Thus, the MONW phenotype developed at a young age is linked to cognitive dysfunction, which is reflected at the transcriptomic level in PBMCs. Neonatal leptin intake can partly counteract this impaired cognition resulting from early HFD consumption.
高脂肪饮食（HFD）和肥胖与认知障碍有关。在这里，我们旨在研究年轻时通过 HFD 诱导的代谢肥胖正常体重（MONW）表型是否也会导致认知功能障碍，并评估新生儿摄入瘦素的潜在认知益处。为此，Wistar 大鼠在哺乳期经口给予瘦素或其载体的生理剂量，随后在断奶后进行 11 周的 HFD 或对照饮食的配对喂养。使用 T 迷宫评估工作记忆，使用实时 RT-qPCR 评估海马体和外周血单核细胞（PBMC）中的基因表达，以鉴定认知生物标志物。年轻的 MONW 样大鼠表现出海马体基因表达变化和工作记忆下降。在哺乳期接受瘦素的动物表现出相似的基因表达变化，但尽管摄入 HFD，仍能保留工作记忆，这部分是由于胰岛素敏感性提高。值得注意的是，PBMC 表达似乎是认知健康的一种可及的生物标志物，反映了尽管没有肥胖，但年轻时 HFD 摄入的有害影响，以及新生儿瘦素治疗对认知的积极影响。因此，在年轻时发展起来的 MONW 表型与认知功能障碍有关，这在 PBMC 的转录组水平上得到反映。新生儿瘦素摄入可以部分抵消因早期 HFD 摄入而导致的认知障碍。
