FGF21 improves cognition by restored synaptic plasticity, dendritic spine density, brain mitochondrial function and cell apoptosis in obese-insulin resistant male rats
FGF21 improves cognition by restored synaptic plasticity, dendritic spine density, brain mitochondrial function and cell apoptosis in obese-insulin resistant male rats
复制标题
DOI：
10.1016/j.yhbeh.2016.08.006
复制
发表时间：
2016-09-01
影响因子：
3.5
通讯作者：
Chattipakorn, Siriporn C.
中科院分区：
文献类型：
--
作者：
Sa-nguanmoo, Piangkwan;Tanajak, Pongpan;Chattipakorn, Siriporn C.
成纤维细胞生长因子21（FGF21）是一种内分泌激素，在肥胖和糖尿病模型中对代谢调节发挥有益作用。然而，FGF 21对肥胖胰岛素抵抗大鼠认知的影响尚未研究。我们假设FGF 21通过改善海马突触可塑性、树突棘密度、脑线粒体功能和脑FGF 21信号传导以及减少脑细胞凋亡来预防肥胖胰岛素抵抗大鼠的认知功能下降。雄性Wistar大鼠18只，随机分为正常饮食组（n = 6）和高脂饮食组（n = 12）。在第13周，将HFD喂养的大鼠再分成两个亚组（n = 6/亚组），以接受载体或重组人FGF 21（0.1 mg/kg/天），持续四周。ND喂养的大鼠给予媒介物四周。在治疗结束时，测定认知功能、代谢参数、促炎标志物、脑线粒体功能、细胞凋亡、海马突触可塑性、树突棘密度和脑FGF 21信号传导。结果表明，赋形剂治疗的HFD喂养大鼠出现肥胖胰岛素抵抗和认知能力下降，海马突触可塑性受损，树突棘密度降低，脑线粒体功能障碍和脑细胞凋亡增加。在这些肥胖胰岛素抵抗大鼠中发现脑FGF 21信号传导受损。FGF21治疗的肥胖胰岛素抵抗大鼠改善了外周胰岛素敏感性，增加了海马突触可塑性，增加了树突棘密度，恢复了脑线粒体功能，减弱了脑细胞凋亡，增加了脑FGF21信号传导，从而预防了认知能力下降。这些发现表明FGF 21治疗在肥胖胰岛素抵抗大鼠中发挥神经保护作用。(C)2016 Elsevier Inc. All rights reserved.
Fibroblast growth factor 21 (FGF21) is an endocrine hormone which exerts beneficial effects on metabolic regulation in obese and diabetic models. However, the effect of FGF21 on cognition in obese-insulin resistant rats has not been investigated. We hypothesized that FGF21 prevented cognitive decline in obese-insulin resistant rats by improving hippocampal synaptic plasticity, dendritic spine density, brain mitochondrial function and brain FGF21 signaling as well as decreasing brain cell apoptosis. Eighteen male Wistar rats were divided into two groups, and received either a normal diet (ND) (n = 6) or a high fat diet (HFD) (n = 12) for 12 weeks. At week 13, the HFD-fed rats were subdivided into two subgroups (n = 6/subgroup) to receive either vehicle or recombinant human FGF21 (0.1 mg/kg/day) for four weeks. ND-fed rats were given vehicle for four weeks. At the end of the treatment, cognitive function, metabolic parameters, pro-inflammatory markers, brain mitochondrial function, cell apoptosis, hippocampal synaptic plasticity, dendritic spine density and brain FGF21 signaling were determined. The results showed that vehicle-treated HFD-fed rats developed obese-insulin resistance and cognitive decline with impaired hippocampal synaptic plasticity, decreased dendritic spine density, brain mitochondrial dysfunction and increased brain cell apoptosis. Impaired brain FGF 21 signaling was found in these obese insulin resistant rats. FGF21-treated obese-insulin resistant rats had improved peripheral insulin sensitivity, increased hippocampal synaptic plasticity, increased dendritic spine density, restored brain mitochondrial function, attenuated brain cells apoptosis and increased brain FGF21 signaling, leading to a prevention of cognitive decline. These findings suggest that FGF21 treatment exerts neuroprotection in obese -insulin resistant rats. (C) 2016 Elsevier Inc. All rights reserved.