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Milena Fioravante, Bruna Bombassaro, Albina F Ramalho, Nathalia R Dragano, Joseane Morari, Carina Solon, Natalia Tobar, Celso D Ramos, Licio A Velloso
Laboratory of Cell Signaling, University of Campinas, Campinas, São Paulo, 13084-970, Brazil.
Department of Radiology, University of Campinas, Campinas, São Paulo, 13084-970, Brazil.
J Neuroinflammation. 2017 Sep 2;14(1):178. doi: 10.1186/s12974-017-0956-9.
The consumption of large amounts of dietary fats can trigger an inflammatory response in the hypothalamus and contribute to the dysfunctional control of caloric intake and energy expenditure commonly present in obesity. The objective of this study was to identify chemokine-related transcripts that could be involved in the early stages of diet-induced hypothalamic inflammation.
We used immunoblot, PCR array, real-time PCR, immunofluorescence staining, glucose and insulin tolerance tests, and determination of general metabolic parameters to evaluate markers of inflammation, body mass variation, and glucose tolerance in mice fed a high-fat diet.
Using a real-time PCR array, we identified leukemia inhibitory factor as a chemokine/cytokine undergoing a rapid increase in the hypothalamus of obesity-resistant and a rapid decrease in the hypothalamus of obesity-prone mice fed a high-fat diet for 1 day. We hypothesized that the increased hypothalamic expression of leukemia inhibitory factor could contribute to the protective phenotype of obesity-resistant mice. To test this hypothesis, we immunoneutralized hypothalamic leukemia inhibitory factor and evaluated inflammatory and metabolic parameters. The immunoneutralization of leukemia inhibitory factor in the hypothalamus of obesity-resistant mice resulted in increased body mass gain and increased adiposity. Body mass gain was mostly due to increased caloric intake and reduced spontaneous physical activity. This modification in the phenotype was accompanied by increased expression of inflammatory cytokines in the hypothalamus. In addition, the inhibition of hypothalamic leukemia inhibitory factor was accompanied by glucose intolerance and insulin resistance.
Hypothalamic expression of leukemia inhibitory factor may protect mice from the development of diet-induced obesity; the inhibition of this protein in the hypothalamus transforms obesity-resistant into obesity-prone mice.
大量食用膳食脂肪会在下丘脑引发炎症反应，并导致热量摄入和能量消耗的功能障碍，这在肥胖中很常见。本研究旨在确定可能参与饮食诱导的下丘脑炎症早期阶段的趋化因子相关转录本。
我们使用免疫印迹、PCR 阵列、实时 PCR、免疫荧光染色、葡萄糖和胰岛素耐量试验以及一般代谢参数的测定来评估肥胖抵抗和肥胖易感小鼠喂食高脂肪饮食后炎症标志物、体重变化和葡萄糖耐量的变化。
使用实时 PCR 阵列，我们发现白血病抑制因子作为一种趋化因子/细胞因子，在肥胖抵抗小鼠的下丘脑中迅速增加，而在肥胖易感小鼠的下丘脑中迅速减少，这些小鼠在喂食高脂肪饮食 1 天后。我们假设，白血病抑制因子在下丘脑中的表达增加可能有助于肥胖抵抗小鼠的保护表型。为了验证这一假设，我们免疫中和了下丘脑白血病抑制因子并评估了炎症和代谢参数。肥胖抵抗小鼠下丘脑白血病抑制因子的免疫中和导致体重增加和肥胖增加。体重增加主要是由于热量摄入增加和自发体力活动减少。这种表型的改变伴随着下丘脑炎症细胞因子表达的增加。此外，下丘脑白血病抑制因子的抑制伴随着葡萄糖不耐受和胰岛素抵抗。
白血病抑制因子在下丘脑的表达可能会保护小鼠免受饮食诱导肥胖的发展；抑制该蛋白在下丘脑中会使肥胖抵抗型小鼠转变为肥胖易感型小鼠。
