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

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Abstract

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.

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Acknowledgements

This work was supported by Basic Science Research Program through the NRF funded by the Ministry of Education (2018R1D1A1B07041643).

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Author notes

  1. L.M. and J.Y. and J.K. contributed equally to this work.

Authors and Affiliations

  1. Department of Food Science and Nutrition, University of Ulsan, Ulsan, 44610, Korea

    Luthfiyyah Mutsnaini, Jihyeon Yang, Jiye Kim, Chu-Sook Kim & Rina Yu

  2. Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, 05505, Korea

    Chan-Hee Lee

  3. Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul, 05505, Korea

    Min-Seon Kim

  4. Department of Food and Nutrition, Yonsei University, Seoul, 03722, Korea

    Taesun Park

  5. Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Japan

    Tsuyoshi Goto

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  1. Luthfiyyah Mutsnaini
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Correspondence to Rina Yu.

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All animal cares and procedures were conducted according to protocols and guidelines approved by the animal care committee of the University of Ulsan, South Korea (LNY-16-010). And no informed consent was required for this study.

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Mutsnaini, L., Yang, J., Kim, J. et al. Filbertone Protects Obesity-induced Hypothalamic Inflammation by Reduction of Microglia-mediated Inflammatory Responses. Biotechnol Bioproc E 26, 86–92 (2021). https://doi.org/10.1007/s12257-020-0220-5

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