High-Fat Diet Induces Apoptosis of Hypothalamic Neurons

被引:305
作者
Moraes, Juliana C. [1 ]
Coope, Andressa [1 ]
Morari, Joseane [1 ]
Cintra, Dennys E. [1 ]
Roman, Erika A. [1 ]
Pauli, Jose R. [1 ]
Romanatto, Talita [1 ]
Carvalheira, Jose B. [1 ]
Oliveira, Alexandre L. R. [2 ]
Saad, Mario J. [1 ]
Velloso, Licio A. [1 ]
机构
[1] Univ Estadual Campinas, Dept Internal Med, Campinas, SP, Brazil
[2] Univ Estadual Campinas, Dept Anat, Campinas, SP, Brazil
来源
PLOS ONE | 2009年 / 4卷 / 04期
关键词
D O I
10.1371/journal.pone.0005045
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Consumption of dietary fats is amongst the most important environmental factors leading to obesity. In rodents, the consumption of fat-rich diets blunts leptin and insulin anorexigenic signaling in the hypothalamus by a mechanism dependent on the in situ activation of inflammation. Since inflammatory signal transduction can lead to the activation of apoptotic signaling pathways, we evaluated the effect of high-fat feeding on the induction of apoptosis of hypothalamic cells. Here, we show that consumption of dietary fats induce apoptosis of neurons and a reduction of synaptic inputs in the arcuate nucleus and lateral hypothalamus. This effect is dependent upon diet composition, and not on caloric intake, since pair-feeding is not sufficient to reduce the expression of apoptotic markers. The presence of an intact TLR4 receptor, protects cells from further apoptotic signals. In diet-induced inflammation of the hypothalamus, TLR4 exerts a dual function, on one side activating pro-inflammatory pathways that play a central role in the development of resistance to leptin and insulin, and on the other side restraining further damage by controlling the apoptotic activity.
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页数:11
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