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高脂肪饮食诱导的代谢综合征 NMRI 小鼠模型:聚焦脑源性神经营养因子(BDNF)。

A high-fat diet induced NMRI mouse model of metabolic syndrome: focus on brain-derived neurotrophic factor (BDNF).

机构信息

Laboratory of Molecular and Cellular Biology 1214, Department of Basic Veterinary Sciences, School of Veterinary Medicine, Razi University, Kermanshah, Islamic Republic of Iran.

Department of Biology, Faculty of Science, Razi University, Kermanshah, 67149-67346, Islamic Republic of Iran.

出版信息

Metab Brain Dis. 2018 Oct;33(5):1635-1640. doi: 10.1007/s11011-018-0271-x. Epub 2018 Jun 25.

Abstract

The association of brain-derived neurotrophic factor (BDNF) as a member of neurotrophin family and metabolic syndrome (MetS) has been proposed, however basic evidence necessary to prove (or disprove) this association in non-genetic animal model is rare. Therefore, we investigated the alteration of encephalic BDNF gene expression in a mouse model of high-fat diet (HFD) induced MetS. To translate MetS, male NMRI mice (9 weeks old; N = 13) fed on a HFD including suet powder (37.50%) and granulated sugar (19.85%) while control mice were fed a diet contained suet powder (6.25%) and granulated sugar (49.09%). We monitored the development of MetS by measuring fasting blood sugar (FBS) and lipid (total cholesterol (TC) and triacylglycerol (TGs)) and lipoprotein (high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol (VLDL-C)) profiles, atherogenic index (AI), and somatic indices after 1 and 3 months of dietary interventions. The HFD intake led to increased body weight, liver weight, FBS, TC, and decreased HDL-C as compared to chow diet in mice after first month of dietary intervention. The increased FBS, body weight, abdominal fat mass, TGs, TC, and VLDL-C and decreased HDL-C were observed in HFD-fed mice as compared to those of chow-fed mice at 3th month. The statistical comparison of two HFD groups in two time intervals of 1st and 3th month confirmed that our HFD-induced MetS model was reliable because FBS, TGs and VLDL-C, TC, and AI have been increased significantly during selected time intervals. The AI increased significantly in HFD-fed mice compared to chow-fed mice after 3 months. The AI in HFD-fed mice treated with HFD for 3 months was increased significantly as compared to mice fed HFD for 1 month. Our diet-induced model more closely mimics the changes observed in human MetS and showed that encephalic BDNF gene in mice fed HFD was under-expressed by 0.30 fold with respect to chow-fed mice after 3 months of dietary intervention.

摘要

脑源性神经营养因子(BDNF)作为神经生长因子家族的一员与代谢综合征(MetS)之间的相关性已经被提出,然而在非遗传动物模型中证明(或证否)这种相关性的基本证据却很少。因此,我们在高脂肪饮食(HFD)诱导的 MetS 小鼠模型中研究了大脑 BDNF 基因表达的变化。为了模拟 MetS,雄性 NMRI 小鼠(9 周龄;N=13)喂食含动物脂肪粉(37.50%)和砂糖(19.85%)的 HFD,而对照组喂食含动物脂肪粉(6.25%)和砂糖(49.09%)的饮食。我们通过测量空腹血糖(FBS)和血脂(总胆固醇(TC)和三酰甘油(TGs))和脂蛋白(高密度脂蛋白胆固醇(HDL-C),极低密度脂蛋白胆固醇(VLDL-C))谱、动脉粥样硬化指数(AI)以及 1 和 3 个月饮食干预后的体指数来监测 MetS 的发展。与对照饮食相比,高脂肪饮食摄入导致小鼠在饮食干预的第一个月体重、肝重、FBS、TC 和 HDL-C 增加。与对照饮食相比,高脂肪饮食喂养的小鼠在第 3 个月时 FBS、体重、腹部脂肪质量、TGs、TC 和 VLDL-C 增加,而 HDL-C 降低。在 1 个月和 3 个月两个时间间隔的两组 HFD 之间的统计学比较证实,我们的 HFD 诱导的 MetS 模型是可靠的,因为 FBS、TG 和 VLDL-C、TC 和 AI 在选定的时间间隔内显著增加。与对照饮食相比,3 个月后 HFD 喂养的小鼠 AI 显著增加。与仅喂食 1 个月 HFD 的小鼠相比,喂食 3 个月 HFD 的小鼠 AI 显著增加。我们的饮食诱导模型更紧密地模拟了人类 MetS 中观察到的变化,并表明喂食 HFD 3 个月后的小鼠大脑 BDNF 基因表达相对于对照饮食组降低了 0.30 倍。

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