Department of Nutrition, UNC Greensboro, Greensboro, NC, USA.
Wake Forest School of Medicine, Physiology and Pharmacology, Winston-Salem, NC, USA.
Nutr Neurosci. 2023 Sep;26(9):864-874. doi: 10.1080/1028415X.2022.2103613. Epub 2022 Jul 28.
Chronic low-grade inflammation is associated with a state of diet-induced obesity that impacts systemic tissues and can cross the blood-brain barrier to act directly on the brain. The extent to which pro-inflammatory cytokines released in these conditions affect dopamine presynaptic neurotransmission has not been previously investigated. The purpose of this study was to examine how dopamine terminals are affected by pro-inflammatory cytokines, and to determine if dietary fat consumption potentiates cytokine effects on dopamine release and reuptake rate in the nucleus accumbens (NAc). Male and female C57BL/6J mice were fed high, medium, or low-fat diets (60%, 30%, or 10% total kcals from fat, respectively) for six weeks. Fast scan cyclic voltammetry (FSCV) was used to measure dopamine release and reuptake rate in the NAc core from coronal brain slices. Electrically evoked dopamine release and the maximal rate of dopamine reuptake () were significantly lower in mice fed the 30% and 60% high-fat diets compared to the 10% low-fat group ( < 0.05). IL-6 5 or 10 nM or TNFα 30 or 300 nM was added to artificial cerebrospinal fluid (aCSF) bathed over brain slices during FSCV. No effect on dopamine release or was observed with lower concentrations. However, 10 nM IL-6 and 300 nM TNFα significantly reduced dopamine release in the 60% fat group ( < 0.05). No effect of added cytokine was observed on . Overall, these data provide evidence that dietary fat increases neural responsiveness to cytokines, which may help inform comorbidities between diet-induced obesity and depression or other mood disorders.
慢性低度炎症与饮食诱导肥胖有关，这种肥胖会影响全身组织，并能穿过血脑屏障直接作用于大脑。目前还没有研究过这些条件下释放的促炎细胞因子对多巴胺前突触神经传递的影响程度。本研究的目的是研究促炎细胞因子如何影响多巴胺末梢，并确定膳食脂肪的消耗是否会增强细胞因子对伏隔核（NAc）中多巴胺释放和再摄取率的影响。雄性和雌性 C57BL/6J 小鼠分别用高脂肪、中脂肪或低脂肪饮食（分别为 60%、30%或 10%总热量来自脂肪）喂养 6 周。快速扫描循环伏安法（FSCV）用于测量冠状脑切片中 NAc 核心的多巴胺释放和再摄取率。与 10%低脂组相比，喂食 30%和 60%高脂肪饮食的小鼠的电诱发多巴胺释放和多巴胺最大再摄取率（）显著降低（<0.05）。在 FSCV 期间，将 5 或 10 nM IL-6 或 30 或 300 nM TNFα 添加到人工脑脊液（aCSF）中。较低浓度对多巴胺释放或无影响。然而，10 nM IL-6 和 300 nM TNFα 显著降低了 60%脂肪组的多巴胺释放（<0.05）。添加细胞因子对无影响。总之，这些数据提供了证据表明，饮食中的脂肪会增加神经对细胞因子的反应性，这可能有助于解释饮食诱导的肥胖与抑郁或其他情绪障碍之间的共病。
