Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
Physiol Behav. 2012 Jun 25;106(4):485-90. doi: 10.1016/j.physbeh.2012.03.021. Epub 2012 Mar 29.
Hypothalamic inflammation is a potentially important process in the pathogenesis of high-fat diet-induced metabolic disorders that has recently received significant attention. Microglia are macrophage-like cells of the central nervous system which are activated by pro-inflammatory signals causing local production of specific interleukins and cytokines, and these in turn may further promote systemic metabolic disease. Whether or how this microglial activation can be averted or reversed is unknown. Since running exercise improves systemic metabolic health and has been found to promote neuronal survival as well as the recovery of brain functions after injury, we hypothesized that regular treadmill running may blunt the effect of western diet on hypothalamic inflammation. Using low-density lipoprotein receptor deficient (l dlr-/-) mice to better reflect human lipid metabolism, we first confirmed that microglial activation in the hypothalamus is severely increased upon exposure to a high-fat, or "western", diet. Moderate, but regular, treadmill running exercise markedly decreased hypothalamic inflammation in these mice. Furthermore, the observed decline in microglial activation was associated with an improvement of glucose tolerance. Our findings support the hypothesis that hypothalamic inflammation can be reversed by exercise and suggest that interventions to avert or reverse neuronal damage may offer relevant potential in obesity treatment and prevention.
下丘脑炎症是高脂肪饮食诱导代谢紊乱发病机制中的一个重要过程，最近受到了广泛关注。小胶质细胞是中枢神经系统中的巨噬细胞样细胞，可被促炎信号激活，导致特定白细胞介素和细胞因子的局部产生，而这些反过来又可能进一步促进全身代谢疾病。这种小胶质细胞的激活是否可以避免或逆转尚不清楚。由于跑步运动可以改善全身代谢健康，并已被发现促进神经元存活以及损伤后大脑功能的恢复，因此我们假设定期进行跑步机跑步可能会减轻西式饮食对下丘脑炎症的影响。使用低密度脂蛋白受体缺陷（ldlr-/-）小鼠来更好地反映人类的脂质代谢，我们首先证实，暴露于高脂肪或“西式”饮食会严重增加下丘脑的小胶质细胞激活。适度但有规律的跑步机运动可显著降低这些小鼠下丘脑的炎症。此外，观察到的小胶质细胞激活下降与葡萄糖耐量的改善有关。我们的研究结果支持下丘脑炎症可以通过运动逆转的假设，并表明避免或逆转神经元损伤的干预措施可能为肥胖症的治疗和预防提供相关的潜力。
