Biotechnology and Bioprocess Engineering 2021; 26(1): 86-92  
Filbertone Protects Obesity-induced Hypothalamic Inflammation by Reduction of Microglia-mediated Inflammatory Responses
Luthfiyyah Mutsnaini, Jihyeon Yang, Jiye Kim, Chu-Sook Kim, Chan-Hee Lee, Min-Seon Kim, Taesun Park, Tsuyoshi Goto, and Rina Yu
Luthfiyyah Mutsnaini, Jihyeon Yang, Jiye Kim, Chu-Sook Kim, Rina Yu*
Department of Food Science and Nutrition, University of Ulsan, Ulsan 44610, Korea
Tel: +82-52-259-2372; Fax: +82-52-259-1698
E-mail: rinayu@ulsan.ac.kr
Chan-Hee Lee
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea
Min-Seon Kim
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center and University of Ulsan College of Medicine, Seoul 05505, Korea
Taesun Park
Department of Food and Nutrition, Yonsei University, Seoul 03722, Korea
Tsuyoshi Goto
Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Japan
L.M. and J.Y. and J.K. contributed equally to this work.
Received: July 10, 2020; Revised: August 31, 2020; Accepted: August 31, 2020; Published online: February 28, 2021.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: filbertone, hypothalamus, inflammation, microglia, obesity


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