Joint Service of Life's Imaging Platform, University of Lille, UDSL, Lille, France.
Inserm, CHU Lille, U1171 - Degenerative & Vascular Cognitive Disorders, University of Lille, F-59000, Lille, France.
Metab Brain Dis. 2018 Feb;33(1):63-77. doi: 10.1007/s11011-017-0133-y. Epub 2017 Oct 16.
Antipsychotics, such as risperidone, increase food intake and induce alteration in glucose and lipid metabolism concomitantly with overweight and body fat increase, these biological abnormalities belong to the metabolic syndrome definition (high visceral adiposity, hypertriglyceridemia, hyperglycemia, low HDL-cholesterol and high blood pressure). Curcumin is a major component of traditional turmeric (Curcuma longa) which has been reported to improve lipid and glucose metabolism and to decrease weight in obese mice. We questioned the potential capacity of curcumin, contained in Curcuma longa extract (Biocurcuma™), to attenuate the risperidone-induced metabolic dysfunction. Two groups of mice were treated once a week, for 22 weeks, with intraperitoneal injection of risperidone (Risperdal) at a dose 12.5 mpk. Two other groups received intraperitoneal injection of the vehicle of Risperdal following the same schedule. Mice of one risperidone-treated groups and of one of vehicle-treated groups were fed a diet with 0.05% Biocurcuma™ (curcumin), while mice of the two other groups received the standard diet. Curcumin limited the capacity of risperidone to reduce spontaneous motricity, but failed to impede risperidone-induced increase in food intake. Curcumin did not reduce the capacity of risperidone to induce weight gain, but decreased visceral adiposity and decreased the risperidone-induced hepatomegaly, but not steatosis. Furthermore, curcumin repressed the capacity of risperidone to induce the hepatic over expression of enzymes involved in lipid metabolism (LXRα, FAS, ACC1, LPL, PPARγ, ACO, SREBP2) and decreased risperidone-induced glucose intolerance and hypertriglyceridemia. Curcumin decreased risperidone-induced increases in serum markers of hepatotoxicity (ALAT, ASAT), as well as of one major hepatic pro-inflammatory transcription factor (NFκB: p105 mRNA and p65 protein). These findings support that nutritional doses of curcumin contained in Curcuma longa extract are able to partially counteract the risperidone-induced metabolic dysfunction in mice, suggesting that curcumin ought to be tested to reduce the capacity of risperidone to induce the metabolic syndrome in human.
抗精神病药，如利培酮，会增加食物摄入，并伴随着超重和体脂肪增加导致葡萄糖和脂质代谢改变，这些生物异常属于代谢综合征的定义（内脏脂肪过多、高三酰甘油血症、高血糖、低高密度脂蛋白胆固醇和高血压）。姜黄素是传统姜黄（Curcuma longa）的主要成分之一，据报道，它能改善肥胖小鼠的脂质和葡萄糖代谢，并减轻体重。我们质疑姜黄（Curcuma longa 提取物（Biocurcuma™）中所含的姜黄素）是否有能力减轻利培酮引起的代谢功能障碍。两组小鼠每周接受一次腹腔注射利培酮（Risperdal），剂量为 12.5mpk。另外两组按相同方案接受利培酮载体的腹腔注射。一组利培酮治疗组和一组载体治疗组的小鼠喂食含 0.05%Biocurcuma™（姜黄素）的饮食，而另外两组的小鼠则喂食标准饮食。姜黄素限制了利培酮降低自发运动能力的能力，但未能阻止利培酮引起的食物摄入量增加。姜黄素并没有降低利培酮诱导体重增加的能力，但减少了内脏脂肪，并减少了利培酮诱导的肝肿大，但没有脂肪变性。此外，姜黄素抑制了利培酮诱导脂质代谢相关酶（LXRα、FAS、ACC1、LPL、PPARγ、ACO、SREBP2）在肝脏中的过度表达，并降低了利培酮诱导的葡萄糖不耐受和高三酰甘油血症。姜黄素降低了利培酮诱导的血清肝毒性标志物（ALAT、ASAT）以及主要的肝前炎症转录因子（NFκB：p105mRNA 和 p65 蛋白）的增加。这些发现支持姜黄（Curcuma longa 提取物中的营养剂量）能够部分抵消利培酮在小鼠中引起的代谢功能障碍，这表明应该测试姜黄素是否能够降低利培酮在人类中引起代谢综合征的能力。
