Diabetes and Obesity Center of Excellence (K.E.B., S.J.G., J.P.T., M.W.S.) and Departments of Medicine (E.A.S., S.J.M.) and Radiology (D.L.), University of Washington, Seattle, Washington 98109.
Endocrinology. 2014 Aug;155(8):2858-67. doi: 10.1210/en.2014-1121. Epub 2014 Jun 10.
Gliosis, the activation of astrocyte and microglial cell populations, is a hallmark of central nervous system injury and is detectable using either immunohistochemistry or in vivo magnetic resonance imaging (MRI). Obesity in rodents and humans is associated with gliosis of the arcuate nucleus, a key hypothalamic region for the regulation of energy homeostasis and adiposity, but whether this response is permanent or reversible is unknown. Here we combine terminal immunohistochemistry analysis with serial, noninvasive MRI to characterize the progression and reversibility of hypothalamic gliosis in high-fat diet (HFD)-fed mice. The effects of HFD feeding for 16 weeks to increase body weight and adiposity relative to chow were nearly normalized after the return to chow feeding for an additional 4 weeks in the diet-reversal group. Mice maintained on the HFD for the full 20-week study period experienced continued weight gain associated with the expected increases of astrocyte and microglial activation in the arcuate nucleus, but these changes were not observed in the diet-reversal group. The proopiomelanocortin neuron number did not differ between groups. Although MRI demonstrated a positive correlation between body weight, adiposity, and the gliosis-associated T2 signal in the mediobasal hypothalamus, it did not detect the reversal of gliosis among the HFD-fed mice after the return to chow diet. We conclude that hypothalamic gliosis associated with 16-week HFD feeding is largely reversible in rodents, consistent with the reversal of the HFD-induced obesity phenotype, and extend published evidence regarding the utility of MRI as a tool for studying obesity-associated hypothalamic gliosis in vivo.
神经胶质增生，即星形胶质细胞和小胶质细胞群体的激活，是中枢神经系统损伤的一个标志，可以通过免疫组织化学或体内磁共振成像（MRI）检测到。肥胖与弓状核的神经胶质增生有关，弓状核是调节能量平衡和肥胖的关键下丘脑区域，但这种反应是永久性的还是可逆的尚不清楚。在这里，我们结合末端免疫组织化学分析和连续的、非侵入性的 MRI，来描述高脂肪饮食（HFD）喂养小鼠下丘脑神经胶质增生的进展和可逆性。在饮食逆转组中，HFD 喂养 16 周导致体重和肥胖增加，与 Chow 喂养相比，在恢复 Chow 喂养额外 4 周后，几乎恢复正常。在整个 20 周研究期间持续接受 HFD 喂养的小鼠体重持续增加，与弓状核中星形胶质细胞和小胶质细胞激活的预期增加相关，但在饮食逆转组中未观察到这些变化。促黑激素原神经元数量在各组之间没有差异。尽管 MRI 显示体重、肥胖和中基底下丘脑与神经胶质增生相关的 T2 信号之间存在正相关，但它没有检测到在恢复 Chow 饮食后 HFD 喂养小鼠的神经胶质增生逆转。我们得出结论，与 16 周 HFD 喂养相关的下丘脑神经胶质增生在啮齿动物中很大程度上是可逆的，这与 HFD 诱导的肥胖表型的逆转一致，并扩展了关于 MRI 作为研究肥胖相关下丘脑神经胶质增生的体内工具的有效性的已发表证据。
