De Paula Gabriela C, Aldana Blanca I, Battistella Roberta, Fernández-Calle Rosalía, Bjure Andreas, Lundgaard Iben, Deierborg Tomas, Duarte João M N
Department of Experimental Medical Science (EMV), Faculty of Medicine, Lund University, Sölvegatan 19, BMC C11, Lund, 221 84, Sweden.
Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
J Neuroinflammation. 2024 Jul 16;21(1):173. doi: 10.1186/s12974-024-03168-7.
Dietary patterns that include an excess of foods rich in saturated fat are associated with brain dysfunction. Although microgliosis has been proposed to play a key role in the development of brain dysfunction in diet-induced obesity (DIO), neuroinflammation with cytokine over-expression is not always observed. Thus, mechanisms by which microglia contribute to brain impairment in DIO are uncertain. Using the BV2 cell model, we investigated the gliosis profile of microglia exposed to palmitate (200 µmol/L), a saturated fatty acid abundant in high-fat diet and in the brain of obese individuals. We observed that microglia respond to a 24-hour palmitate exposure with increased proliferation, and with a metabolic network rearrangement that favors energy production from glycolysis rather than oxidative metabolism, despite stimulated mitochondria biogenesis. In addition, while palmitate did not induce increased cytokine expression, it modified the protein cargo of released extracellular vesicles (EVs). When administered intra-cerebroventricularly to mice, EVs secreted from palmitate-exposed microglia in vitro led to memory impairment, depression-like behavior, and glucose intolerance, when compared to mice receiving EVs from vehicle-treated microglia. We conclude that microglia exposed to palmitate can mediate brain dysfunction through the cargo of shed EVs.
富含饱和脂肪的食物摄入过量的饮食模式与脑功能障碍有关。尽管有人提出小胶质细胞增生在饮食诱导的肥胖（DIO）所致脑功能障碍的发展中起关键作用，但并非总能观察到伴有细胞因子过度表达的神经炎症。因此，小胶质细胞导致DIO脑损伤的机制尚不清楚。我们使用BV2细胞模型，研究了暴露于棕榈酸（200 µmol/L）的小胶质细胞的胶质细胞增生情况，棕榈酸是一种在高脂饮食和肥胖个体大脑中大量存在的饱和脂肪酸。我们观察到，小胶质细胞在暴露于棕榈酸24小时后，增殖增加，代谢网络重排，尽管线粒体生物发生受到刺激，但更倾向于通过糖酵解而非氧化代谢产生能量。此外，虽然棕榈酸没有诱导细胞因子表达增加，但它改变了释放的细胞外囊泡（EVs）的蛋白质成分。与接受来自用溶剂处理的小胶质细胞的细胞外囊泡的小鼠相比，体外暴露于棕榈酸的小胶质细胞分泌的细胞外囊泡经脑室内注射给小鼠后，会导致记忆障碍、抑郁样行为和葡萄糖不耐受。我们得出结论，暴露于棕榈酸的小胶质细胞可通过脱落的细胞外囊泡的成分介导脑功能障碍。
