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胡椒碱可减轻高脂饮食诱导的斯普拉格-道利大鼠肥胖中的肝脏脂肪变性和胰岛素抵抗。

Piperine attenuates hepatic steatosis and insulin resistance in high-fat diet-induced obesity in Sprague-Dawley rats.

作者信息

Wang Xiong, Zhang Yanhua, Zhang Lei, Wang Wenli, Che Huilian, Zhang Yali

机构信息

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

出版信息

Nutr Res. 2022 Dec;108:9-21. doi: 10.1016/j.nutres.2022.10.007. Epub 2022 Oct 20.

DOI:10.1016/j.nutres.2022.10.007
PMID:36375392
Abstract

Substantial evidence suggests that pepper consumption is associated with a reduced risk of obesity-related complications. However, whether piperine, the main component of pepper, improves obesity-induced hepatic lipid accumulation and insulin resistance and the action mechanism of piperine still remain unclear. We hypothesized that piperine attenuates high-fat diet (HFD)-induced obesity and improves the related metabolic complications in HFD-induced obese rats. Adult Sprague-Dawley (SD) male rats were fed a control diet (CON) or an HFD for 16 weeks. Obese rats were divided into 4 groups: HFD and HFD with daily gavage of piperine 2.7 mg/kg body weight (PIP-Low), 13.5 mg/kg body weight (PIP-Medium), and 27 mg/kg body weight (PIP-High) for another 8 weeks. Rats were euthanized after an 8-hour fast, and the liver, heart, kidney, and white adipose tissue were collected and stored at -80 °C. Piperine administration significantly reduced weight gain, plasma insulin, and glucose concentration. For oral piperine at a dose of 27 mg/kg body weight, body weight significantly decreased by 5.7% compared with that in the HFD group. Additionally, oral piperine administration considerably reduced serum triglyceride concentration. Furthermore, piperine administration reversed the HFD-induced downregulation of adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling molecules and increased the plasma levels of adiponectin and the messenger RNA expression of the adiponectin receptor; additionally, it increased the phosphorylation of phosphatidylinositol-3 kinase (PI3K) and protein kinase B. Overall, oral piperine administration reversed HFD-induced liver lipid accumulation and insulin resistance, possibly via the inactivation of adiponectin-AMPK and PI3K-Akt signaling. These findings imply that piperine could serve as an effective agent for healthy weight loss.

摘要

大量证据表明,食用胡椒与肥胖相关并发症风险降低有关。然而,胡椒的主要成分胡椒碱是否能改善肥胖诱导的肝脏脂质蓄积和胰岛素抵抗,以及胡椒碱的作用机制仍不清楚。我们推测,胡椒碱可减轻高脂饮食(HFD)诱导的肥胖,并改善HFD诱导的肥胖大鼠的相关代谢并发症。将成年Sprague-Dawley(SD)雄性大鼠分为对照组(CON)或给予HFD喂养16周。将肥胖大鼠分为4组:HFD组以及HFD组中每日分别灌胃2.7 mg/kg体重(低剂量胡椒碱组,PIP-Low)、13.5 mg/kg体重(中剂量胡椒碱组,PIP-Medium)和27 mg/kg体重(高剂量胡椒碱组,PIP-High)的胡椒碱,持续8周。禁食8小时后对大鼠实施安乐死,收集肝脏、心脏、肾脏和白色脂肪组织,并储存于-80℃。给予胡椒碱可显著降低体重增加、血浆胰岛素和血糖浓度。对于体重27 mg/kg剂量的口服胡椒碱,与HFD组相比,体重显著下降了5.7%。此外,口服胡椒碱可显著降低血清甘油三酯浓度。此外,给予胡椒碱可逆转HFD诱导的5'-单磷酸腺苷激活蛋白激酶(AMPK)信号分子的下调,并增加脂联素的血浆水平以及脂联素受体的信使核糖核酸表达;此外,它还增加了磷脂酰肌醇-3激酶(PI3K)和蛋白激酶B的磷酸化。总体而言,口服胡椒碱可逆转HFD诱导的肝脏脂质蓄积和胰岛素抵抗,可能是通过脂联素-AMPK和PI3K-Akt信号的失活实现的。这些发现表明,胡椒碱可能是一种有效的健康减肥药物。

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