Microglial activation is critical for obesityinduced hypothalamic inflammation and is closely associated with pathologies of metabolic complications. In this study, we investigated the effect of filbertone, a main aroma compound of hazelnuts, on microglia-mediated inflammatory responses in vitro and obesity-induced hypothalamic inflammation in vivo. BV2 microglial cells were stimulated with lipopolysaccharide (LPS) in the presence or absence of filbertone. Meanwhile, C57BL/6 mice were fed for 10- weeks on a high-fat diet (HFD) supplemented with 0.2% filbertone. Levels of inflammatory mediators in microglia or hypothalamus were measured using enzyme-linked immunosorbent assays or quantitative real-time PCR. Filbertone significantly inhibited nitrite oxide production, inducible nitric oxide synthase expression, and inflammatory cytokine production in LPS-stimulated microglia. Filbertone also inhibited LPS-stimulated activation of inflammatory signaling molecules, mitogen-activated protein kinases (MAPK) such as extracellular signal-regulated kinases and p38, and the degradation of inhibitory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in microglia. Moreover, filbertone supplementation markedly suppressed the expression of inflammatory cytokines and microglia activation marker in the hypothalamus of obese mice fed a HFD. These results suggest that filbertone reduces HFD-induced microglial activation through inhibition of the MAPK and NF-κB pathways, and thus protects obesityinduced hypothalamic inflammation. Filbertone may be useful for protection of microglia-mediated hypothalamic inflammation in obese condition and related metabolic complications.

小胶质细胞激活对于肥胖引起的下丘脑炎症至关重要，并且与代谢并发症的病理密切相关。在这项研究中，我们调查了榛子的主要香气成分非伯酮对小胶质细胞介导的体外炎症反应和体内肥胖引起的下丘脑炎症的影响。在有或没有榛子酮的情况下，用脂多糖（LPS）刺激BV2小胶质细胞。同时，C57BL / 6小鼠在补充0.2％filbertone的高脂饮食（HFD）下喂养10周。小胶质细胞或下丘脑中炎性介质的水平使用酶联免疫吸附测定或实时定量PCR进行测量。榛子酮可显着抑制LPS刺激的小胶质细胞产生亚硝酸盐，诱导型一氧化氮合酶的表达和炎性细胞因子的产生。Filbertone还抑制LPS刺激的炎症信号分子，有丝分裂原激活的蛋白激酶（MAPK）（如细胞外信号调节激酶和p38）的激活以及抑制性核因子kappa轻链增强子（NF）的降解-κB）。而且，补充欧洲榛树酮能显着抑制高脂饮食肥胖小鼠下丘脑炎性细胞因子和小胶质细胞活化标志物的表达。这些结果表明，欧洲榛树酮通过抑制MAPK和NF-κB途径来降低HFD诱导的小胶质细胞活化，从而保护肥胖引起的下丘脑炎症。在肥胖状况和相关的代谢并发症中，非伯酮可能对保护小胶质细胞介导的下丘脑炎症有用。