Herrick Mary K, Favela Kristin M, Simerly Richard B, Abumrad Naji N, Bingham Nathan C
Department of Pediatrics, Vanderbilt University Medical Center, 1500 21 st. Ave South, Suite 1514, Nashville, TN, 37212, USA.
Present address: Department of Physiology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Mol Med. 2018 Oct 24;24(1):56. doi: 10.1186/s10020-018-0057-y.
Exposure of rodents to chronic high-fat diet (HFD) results in upregulation of inflammatory markers and proliferation of microglia within the mediobasal hypothalamus. Such hypothalamic inflammation is associated with metabolic dysfunction, central leptin resistance, and maintenance of obesity. Bariatric surgeries result in long-term stable weight loss and improved metabolic function. However, the effects of such surgical procedures on HFD-induced hypothalamic inflammation are unknown. We sought to characterize the effects of two bariatric surgical procedures, Roux-en-Y gastric bypass (RYGB) and biliary diversion (BD-IL), in female mice with particular emphasis on HFD-induced hypothalamic inflammation and microgliosis.
RYGB and BD-IL were performed on diet-induced obese (DIO) mice. Quantitative RT-PCR and fluorescent microscopy were used to evaluate hypothalamic inflammatory gene expression and microgliosis. Results were compared to lean (CD), DIO sham-surgerized mice (DIO-SHAM), and dietary weight loss (DIO-Rev) controls.
In female mice, RYGB and BD-IL result in normalization of hypothalamic inflammatory gene expression and microgliosis within 8 weeks of surgery, despite ongoing exposure to HFD. Paralleling these results, the hypothalamic expression levels of the orexigenic neuropeptide Agrp and the anorexic response of surgical mice to exogenous leptin were comparable to lean controls (CD). In contrast, results from DIO-Rev mice were comparable to DIO-SHAM mice, despite transition back to standard rodent show and normalization of weight.
Bariatric surgery attenuates HFD-induced hypothalamic inflammation and microgliosis and restores leptin sensitivity, despite ongoing exposure to HFD.
啮齿动物长期食用高脂饮食（HFD）会导致中基底下丘脑内炎症标志物上调和小胶质细胞增殖。这种下丘脑炎症与代谢功能障碍、中枢性瘦素抵抗及肥胖的维持有关。减肥手术可带来长期稳定的体重减轻并改善代谢功能。然而，此类手术对HFD诱导的下丘脑炎症的影响尚不清楚。我们试图描述两种减肥手术，即Roux-en-Y胃旁路术（RYGB）和胆胰分流术（BD-IL）对雌性小鼠的影响，特别关注HFD诱导的下丘脑炎症和小胶质细胞增生。
对饮食诱导肥胖（DIO）小鼠进行RYGB和BD-IL手术。采用定量逆转录聚合酶链反应（qRT-PCR）和荧光显微镜评估下丘脑炎症基因表达和小胶质细胞增生。将结果与瘦小鼠（CD）、DIO假手术小鼠（DIO-SHAM）和饮食减重（DIO-Rev）对照组进行比较。
在雌性小鼠中，尽管持续食用HFD，但RYGB和BD-IL在术后8周内可使下丘脑炎症基因表达和小胶质细胞增生恢复正常。与这些结果相似，促食欲神经肽Agrp的下丘脑表达水平以及手术小鼠对外源性瘦素的厌食反应与瘦对照组（CD）相当。相比之下，DIO-Rev小鼠的结果与DIO-SHAM小鼠相当，尽管它们已恢复至标准啮齿动物饮食且体重恢复正常。
尽管持续食用HFD，但减肥手术可减轻HFD诱导的下丘脑炎症和小胶质细胞增生，并恢复瘦素敏感性。
