Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi Province, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
Department of Digestive Diseases, Xijing Hospital, Xi'an, Shaanxi Province, China.
J Nutr Biochem. 2022 Dec;110:109146. doi: 10.1016/j.jnutbio.2022.109146. Epub 2022 Aug 29.
Alternate-day fasting (ADF) regimen has been reported to alleviate obesity and insulin resistance. However, the effects of ADF on preventing diet-induced non-alcoholic fatty liver disease (NAFLD) and related cognitive deficits are still elusive. In the present study, a high-fat diet (HFD)-induced obese (DIO) C57BL/6 mouse model was established. Mice were treated with a 4-week long ADF regimen and/or switching the diet to a standard diet. ADF reduced lipid accumulation, activated AMPK/ULK1 signaling, and suppressed the phosphorylation of mTOR. Also, ADF inhibited lipid accumulation and inflammatory responses in the white adipose tissue and down-regulated expressions of PPAR-γ and cytokines. Moreover, ADF improved the working memory and synaptic structure in the DIO mice and upregulated PSD-95 and BDNF in the hippocampus. ADF reduced oxidative stress and microglial over-activation in the CNS. These results suggest that ADF attenuates NAFLD development in the liver of DIO mice, which is related to the mediating effects of ADF on autophagy and energy metabolism. ADF also enhanced cognitive function, which could be partly explained by the down-regulated peripheral inflammatory responses. This study indicates that ADF could be a promising intervention for alleviating NAFLD development and cognitive decline.
隔日禁食（ADF）方案已被报道可减轻肥胖和胰岛素抵抗。然而，ADF 预防饮食诱导的非酒精性脂肪性肝病（NAFLD）和相关认知缺陷的作用仍不清楚。在本研究中，建立了高脂肪饮食（HFD）诱导肥胖（DIO）C57BL/6 小鼠模型。用为期 4 周的 ADF 方案和/或将饮食切换为标准饮食对小鼠进行处理。ADF 减少了脂质积累，激活了 AMPK/ULK1 信号通路，并抑制了 mTOR 的磷酸化。此外，ADF 抑制了白色脂肪组织中的脂质积累和炎症反应，并下调了 PPAR-γ 和细胞因子的表达。此外，ADF 改善了 DIO 小鼠的工作记忆和突触结构，并在上皮细胞中上调了 PSD-95 和 BDNF。ADF 减少了中枢神经系统中的氧化应激和小胶质细胞过度激活。这些结果表明，ADF 可减轻 DIO 小鼠肝脏中的 NAFLD 发展，这与 ADF 对自噬和能量代谢的调节作用有关。ADF 还增强了认知功能，这部分可以通过下调外周炎症反应来解释。本研究表明，ADF 可能是一种有前途的干预措施，可减轻 NAFLD 发展和认知能力下降。
