Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide.-猫眼课题宝

DOI：

10.1242/dmm.009068

发表时间：

2012-09

期刊：

Disease models & mechanisms

影响因子：

4.3

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

Lawrence CB;Brough D;Knight EM

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424462/?report=classic

肥胖与感染患病率和严重程度的增加有关。肥胖遗传动物模型（ob/ob 和 db/db 小鼠）表现出中枢介导的疾病行为的改变，以响应脂多糖 (LPS) 等急性炎症刺激。然而，饮食诱导的肥胖 (DIO) 对小鼠对 LPS 的厌食和发热反应的影响尚不清楚。因此，本研究确定了 DIO 和 ob/ob 小鼠如何应对全身炎症挑战。对 C57BL/6 DIO 和 ob/ob 小鼠及其各自的对照小鼠进行腹膜内 (i.p.) 注射 LPS。与对照组相比，DIO 和 ob/ob 小鼠在 8 小时内表现出对 LPS（100 μg/kg）的发热反应改变。与对照小鼠相比，LPS 在 DIO 中引起更大、更持久的厌食作用，并且在 ob/ob 小鼠中，LPS 比对照小鼠更早地诱导食物摄入量和体重减少。 LPS 对肥胖小鼠的这些影响在固定剂量的 LPS（5 μg）后也可见到。 LPS (100 μg/kg) 在对照小鼠的几个脑核中诱导 Fos 蛋白表达，而在肥胖小鼠的大脑中观察到的 Fos 阳性细胞较少。与对照组相比，肥胖小鼠对脂多糖的炎症反应也发生了改变：在肥胖小鼠的血浆、脾脏、肝脏和腹膜巨噬细胞中检测到细胞因子表达和释放的变化。总之，DIO 和 ob/ob 小鼠对全身炎症挑战表现出行为反应和细胞因子释放的改变。这些发现可能有助于解释为什么肥胖的人对感染表现出更高的敏感性。

Obesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice) display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS). However, the effect of diet-induced obesity (DIO) on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p.) injection of LPS. Compared with controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg) over 8 hours. LPS caused a greater and more prolonged anorexic effect in DIO compared with control mice and, in ob/ob mice, LPS induced a reduction in food intake and body weight earlier than it did in controls. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg). LPS (100 μg/kg) induced Fos protein expression in several brain nuclei of control mice, with fewer Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice compared with controls: changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages in obese mice. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show increased sensitivity to infections.