HFD + L" class="article-image">
抽象 高脂肪饮食诱导的代谢变化不仅限于心血管疾病的发作，还包括对与学习和记忆相关的大脑功能的影响。本研究旨在评估代谢功能障碍大鼠模型中的线粒体标志物和功能以及认知功能。对 8 周龄雄性 Wistar 大鼠进行对照饮食或结合高脂饮食 （HFD） 与饮用水中的一氧化氮合酶抑制剂 L-NAME 的 2 次命中方案。HFD 加 L-NAME 诱导肥胖、高血压和血清胆固醇升高。这些大鼠在海马体中表现出生物能量功能障碍，其特征是与 ATP 生成相关的氧 （O2） 消耗减少，H2O2 生成没有变化。此外，OPA1 蛋白在 HFD + L-NAME 大鼠海马体中表达上调，其他形态学相关蛋白无改变。一致地，HFD + L-NAME 大鼠在 Morris 水迷宫参考记忆测试中表现出性能中断。新皮层没有表现出生物能量变化或 H2O2 产生的改变。HFD + L-NAME 大鼠新皮层中的钙摄取率和保留能力没有改变。我们的结果表明，暴露于 HFD 加 L-NAME 的大鼠的海马线粒体生物能量功能受到干扰，从而破坏空间学习，而新皮层功能不受影响。
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Metabolic dysfunction induced by HFD + L-NAME preferentially affects hippocampal mitochondria, impacting spatial memory in rats
Abstract High-fat diet-induced metabolic changes are not restricted to the onset of cardiovascular diseases, but also include effects on brain functions related to learning and memory. This study aimed to evaluate mitochondrial markers and function, as well as cognitive function, in a rat model of metabolic dysfunction. Eight-week-old male Wistar rats were subjected to either a control diet or a two-hit protocol combining a high fat diet (HFD) with the nitric oxide synthase inhibitor L-NAME in the drinking water. HFD plus L-NAME induced obesity, hypertension, and increased serum cholesterol. These rats exhibited bioenergetic dysfunction in the hippocampus, characterized by decreased oxygen (O2) consumption related to ATP production, with no changes in H2O2 production. Furthermore, OPA1 protein expression was upregulated in the hippocampus of HFD + L-NAME rats, with no alterations in other morphology-related proteins. Consistently, HFD + L-NAME rats showed disruption of performance in the Morris Water Maze Reference Memory test. The neocortex did not exhibit either bioenergetic changes or alterations in H2O2 production. Calcium uptake rate and retention capacity in the neocortex of HFD + L-NAME rats were not altered. Our results indicate that hippocampal mitochondrial bioenergetic function is disturbed in rats exposed to a HFD plus L-NAME, thus disrupting spatial learning, whereas neocortical function remains unaffected.