Sodhi Komal, Pratt Rebecca, Wang Xiaoliang, Lakhani Hari Vishal, Pillai Sneha S, Zehra Mishghan, Wang Jiayan, Grover Lawrence, Henderson Brandon, Denvir James, Liu Jiang, Pierre Sandrine, Nelson Thomas, Shapiro Joseph I
Departments of Medicine, Surgery, and Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA.
iScience. 2021 Oct 12;24(11):103262. doi: 10.1016/j.isci.2021.103262. eCollection 2021 Nov 19.
Recent studies suggest that a western diet may contribute to clinical neurodegeneration and dementia. Adipocyte-specific expression of the Na,K-ATPase signaling antagonist, NaKtide, ameliorates the pathophysiological consequences of murine experimental obesity and renal failure. In this study, we found that a western diet produced systemic oxidant stress along with evidence of activation of Na,K-ATPase signaling within both murine brain and peripheral tissues. We also noted this diet caused increases in circulating inflammatory cytokines as well as behavioral, and brain biochemical changes consistent with neurodegeneration. Adipocyte specific NaKtide affected by a doxycycline on/off expression system ameliorated all of these diet effects. These data suggest that a western diet produces cognitive decline and neurodegeneration through augmented Na,K-ATPase signaling and that antagonism of this pathway in adipocytes ameliorates the pathophysiology. If this observation is confirmed in humans, the adipocyte Na,K-ATPase may serve as a clinical target in the therapy of neurodegenerative disorders.
最近的研究表明，西方饮食可能会导致临床神经退行性变和痴呆。钠钾ATP酶信号拮抗剂NaKtide在脂肪细胞中的特异性表达，可改善小鼠实验性肥胖和肾衰竭的病理生理后果。在本研究中，我们发现西方饮食会产生全身性氧化应激，并伴有小鼠大脑和外周组织中钠钾ATP酶信号激活的证据。我们还注意到，这种饮食会导致循环炎症细胞因子增加，以及与神经退行性变一致的行为和脑生化变化。受强力霉素开/关表达系统影响的脂肪细胞特异性NaKtide改善了所有这些饮食效应。这些数据表明，西方饮食通过增强钠钾ATP酶信号导致认知能力下降和神经退行性变，而脂肪细胞中该信号通路的拮抗作用可改善病理生理学。如果这一观察结果在人类中得到证实，脂肪细胞钠钾ATP酶可能成为神经退行性疾病治疗的临床靶点。
