Peripheral adipose tissue insulin resistance alters lipid composition and function of hippocampal synapses.
Peripheral adipose tissue insulin resistance alters lipid composition and function of hippocampal synapses.
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DOI：
10.1111/jnc.13043
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发表时间：
2015-04
影响因子：
4.7
通讯作者：
Abate N
中科院分区：
文献类型：
--
作者：
Sallam HS;Tumurbaatar B;Zhang WR;Tuvdendorj D;Chandalia M;Tempia F;Laezza F;Taglialatela G;Abate N
令人信服的证据表明，2型糖尿病（T2 D）、胰岛素抵抗（IR）和代谢综合征通常伴有认知障碍。然而，这些代谢异常和CNS功能障碍之间的机制联系需要进一步研究。在这里，我们评估是否脂肪组织（AT）IR和相关的代谢改变导致中枢神经系统的变化，通过研究突触脂质的组成和功能的脂肪细胞特异性外核苷酸焦磷酸磷酸二酯酶过表达转基因（AtENPP 1-Tg）小鼠，模型的特点是白色脂肪细胞IR，全身IR，异位脂肪沉积。当喂食高脂饮食（HFD）时，AtENPP 1-Tg小鼠重现了人类代谢综合征的基本特征，使其成为表征外周诱导的CNS缺陷的理想模型。使用气相色谱和蛋白质印迹分析的组合，我们发现的证据改变脂质组成，包括减少磷脂和增加甘油三酯（TG）和脂肪酸（FFA）在海马突触体分离HFD喂养AtENPP 1-Tg小鼠。这些变化与海马角氨1（CA 1）突触的Schaffer侧支基础突触传递受损、GluN 1谷氨酸受体亚基磷酸化降低、胰岛素受体表达下调和FFA受体1上调相关。
Compelling evidence indicates that type 2 diabetes mellitus (T2D), insulin resistance (IR), and metabolic syndrome are often accompanied by cognitive impairment. However, the mechanistic link between these metabolic abnormalities and CNS dysfunction requires further investigations. Here, we evaluated whether adipose tissue (AT) IR and related metabolic alterations resulted in CNS changes by studying synapse lipid composition and function in the adipocyte-specific ecto-nucleotide pyrophosphate phosphodiesterase overexpressing transgenic (AtENPP1-Tg) mouse, a model characterized by white adipocyte IR, systemic IR, and ectopic fat deposition. When fed a high-fat diet (HFD), AtENPP1-Tg mice recapitulate essential features of the human metabolic syndrome, making them an ideal model to characterize peripherally induced CNS deficits. Using a combination of gas chromatography and western blot analysis, we found evidence of altered lipid composition, including decreased phospholipids and increased triglycerides (TG) and fatty acid (FFA) in hippocampal synaptosomes isolated from HFD-fed AtENPP1-Tg mice. These changes were associated with impaired basal synaptic transmission at the Schaffer collaterals to hippocampal cornu ammonis 1 (CA1) synapses, decreased phosphorylation of the GluN1 glutamate receptor subunit, down-regulation of insulin receptor expression and up-regulation of the FFA receptor 1.
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影响因子：
15.1
作者：
Bjorklund NL;Reese LC;Sadagoparamanujam VM;Ghirardi V;Woltjer RL;Taglialatela G
通讯作者：
Taglialatela G
影响因子：
3.7
作者：
Costello DA;Claret M;Al-Qassab H;Plattner F;Irvine EE;Choudhury AI;Giese KP;Withers DJ;Pedarzani P
通讯作者：
Pedarzani P
影响因子：
2.5
作者：
LIU, LF;BROWN, JC;MONAGHAN, DT
通讯作者：
MONAGHAN, DT
DOI：
10.1152/ajpendo.00087.2011
发表时间：
2011-11-01
影响因子：
5.1
作者：
Pan, Wentong;Ciociola, Ester;Abate, Nicola
通讯作者：
Abate, Nicola
影响因子：
13.5
作者：
Lomonaco, Romina;Ortiz-Lopez, Carolina;Cusi, Kenneth
通讯作者：
Cusi, Kenneth