Laboratory of Cell Signaling, University of Campinas, Brazil.
Neuroscience. 2010 Nov 10;170(4):1035-44. doi: 10.1016/j.neuroscience.2010.08.013. Epub 2010 Aug 13.
In diet-induced obesity, hypothalamic inflammation is triggered as an outcome of prolonged exposure to dietary fats. Toll-like receptor 4 (TLR4) activation plays a central role in this process, inducing endoplasmic reticulum stress and activating inflammatory cytokine gene transcription. Although saturated fatty acids can induce endoplasmic reticulum stress in the hypothalamus, it is unknown whether inflammatory cytokines alone can activate this mechanism. Here, rats were treated with TNF-α or lyposaccharide (LPS) and endoplasmic reticulum stress and unfolded protein response were evaluated by immunoblot and polymerase chain reaction (PCR). Activation of TLR4 by LPS was capable of inducing a complete endoplasmic reticulum stress and unfolded protein response through the PERK/eIF2α and IRE1α/XBP1 pathways. Conversely, TNF-α, injected either locally or systemically, was unable to induce a complete program of unfolded protein response, although the activation of endoplasmic reticulum stress was achieved to a certain degree. Thus, in the hypothalamus, the isolated action of TNF-α is insufficient to produce the activation of a complete program of unfolded protein response.
在饮食诱导的肥胖中，由于长期接触膳食脂肪，下丘脑发生炎症反应。Toll 样受体 4（TLR4）的激活在这一过程中起着核心作用，它会诱导内质网应激并激活炎症细胞因子基因转录。虽然饱和脂肪酸可在下丘脑中诱导内质网应激，但尚不清楚单独的炎症细胞因子是否可以激活这种机制。在这里，通过免疫印迹和聚合酶链反应（PCR）评估了 TNF-α或脂多糖（LPS）处理大鼠的内质网应激和未折叠蛋白反应。LPS 激活 TLR4 可通过 PERK/eIF2α 和 IRE1α/XBP1 通路诱导完整的内质网应激和未折叠蛋白反应。相反，局部或全身注射 TNF-α虽然在一定程度上能激活内质网应激，但不能诱导完整的未折叠蛋白反应程序。因此，在下丘脑，TNF-α 的单独作用不足以产生完整的未折叠蛋白反应程序的激活。
