Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, China.
College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.
J Agric Food Chem. 2023 Jun 21;71(24):9404-9418. doi: 10.1021/acs.jafc.3c01524. Epub 2023 Jun 12.
Leucine restriction (LR) improves insulin resistance and promotes white adipose tissue browning. However, the effect of LR on obesity-associated cognitive impairment remains unclear. The present study found that an 8-week LR dramatically improved high-fat diet (HFD)-induced cognitive decline by preventing synaptic dysfunction, increasing the expressions of neurotrophic factors, and inhibiting neuroinflammation in memory-related brain regions. Moreover, LR notably reshaped the structure of gut microbiota, which was manifested by downregulating the Firmicutes/Bacteroidetes ratio, reducing the relative abundance of inflammation-related bacteria including , , , and but increasing short-chain fatty acid (SCFA)-producing bacterial genera including , , , and . Notably, HFD-caused SCFA reduction, gut barrier damage, and LPS leakage were recovered by LR. Our findings suggested that LR could serve as an effective approach to attenuate obesity-induced cognitive deficits, which may be achieved by balancing gut microbiota homeostasis and enhancing SCFA production.
限制亮氨酸摄入（LR）可改善胰岛素抵抗并促进白色脂肪组织褐变。然而，LR 对肥胖相关认知障碍的影响尚不清楚。本研究发现，8 周的 LR 可通过防止突触功能障碍、增加神经营养因子的表达和抑制与记忆相关脑区的神经炎症，显著改善高脂肪饮食（HFD）诱导的认知能力下降。此外，LR 明显重塑了肠道微生物群的结构，表现在下调厚壁菌门/拟杆菌门比值、减少炎症相关细菌（包括 、 、 、 ）的相对丰度，而增加产生短链脂肪酸（SCFA）的细菌属（包括 、 、 、 ）的相对丰度。值得注意的是，LR 恢复了 HFD 引起的 SCFA 减少、肠道屏障损伤和 LPS 渗漏。我们的研究结果表明，LR 可作为一种有效方法来减轻肥胖引起的认知缺陷，其可能通过平衡肠道微生物群的稳态和增强 SCFA 的产生来实现。
