Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity.
Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity.
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DOI：
10.1371/journal.pone.0030571
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Velloso LA
中科院分区：
文献类型：
--
作者：
Cintra DE;Ropelle ER;Moraes JC;Pauli JR;Morari J;Souza CT;Grimaldi R;Stahl M;Carvalheira JB;Saad MJ;Velloso LA
在实验模型中，下丘脑炎症是肥胖发生和发展的早期决定因素。药理学和基因为基础的方法已被证明有效地抑制炎症和纠正肥胖表型。然而，营养素在调节下丘脑炎症中的作用尚不清楚。在这里，我们表明，在饮食诱导肥胖的小鼠模型中，用亚麻籽油（富含C18：3）或橄榄油（富含C18：1）部分替代饮食中的脂肪酸成分，可纠正下丘脑炎症、下丘脑和全身胰岛素抵抗以及身体肥胖。此外，在肥胖大鼠icv注射后，ω3和ω9纯脂肪酸均减少自发性食物摄入和体重增加。这些作用伴随着下丘脑对瘦素/胰岛素的功能性和分子抗性的逆转以及POMC和CART表达的增加。此外，ω3和ω9脂肪酸都抑制AMPK/ACC通路，并增加下丘脑中CPT 1和SCD 1的表达。最后，急性下丘脑注射ω3和ω9脂肪酸通过最近鉴定的GPR 120不饱和脂肪酸受体激活信号转导。不饱和脂肪酸既可以作为营养物质，也可以直接作用于下丘脑，逆转饮食引起的炎症，减少身体肥胖。这些数据表明，除了药理学和遗传学方法外，营养素也可以成为控制肥胖症下丘脑炎症的有吸引力的候选者。
In experimental models, hypothalamic inflammation is an early and determining factor in the installation and progression of obesity. Pharmacological and gene-based approaches have proven efficient in restraining inflammation and correcting the obese phenotypes. However, the role of nutrients in the modulation of hypothalamic inflammation is unknown. Here we show that, in a mouse model of diet-induced obesity, partial substitution of the fatty acid component of the diet by flax seed oil (rich in C18:3) or olive oil (rich in C18:1) corrects hypothalamic inflammation, hypothalamic and whole body insulin resistance, and body adiposity. In addition, upon icv injection in obese rats, both ω3 and ω9 pure fatty acids reduce spontaneous food intake and body mass gain. These effects are accompanied by the reversal of functional and molecular hypothalamic resistance to leptin/insulin and increased POMC and CART expressions. In addition, both, ω3 and ω9 fatty acids inhibit the AMPK/ACC pathway and increase CPT1 and SCD1 expression in the hypothalamus. Finally, acute hypothalamic injection of ω3 and ω9 fatty acids activate signal transduction through the recently identified GPR120 unsaturated fatty acid receptor. Unsaturated fatty acids can act either as nutrients or directly in the hypothalamus, reverting diet-induced inflammation and reducing body adiposity. These data show that, in addition to pharmacological and genetic approaches, nutrients can also be attractive candidates for controlling hypothalamic inflammation in obesity.
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影响因子：
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