Filbertone Protects Obesity-induced Hypothalamic Inflammation by Reduction of Microglia-mediated Inflammatory Responses

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.