Quercetin Protects Obesity-Induced Hypothalamic Inflammation by Reducing Microglia-Mediated Inflammatory Responses via HO-1 Induction

• Published in: Nutrients Vol. 9; no. 7; p. 650
• Main Authors: Yang, Jihyeon, Kim, Chu-Sook, Tu, Thai Hien, Kim, Min-Seon, Goto, Tsuyoshi, Kawada, Teruo, Choi, Myung-Sook, Park, Taesun, Sung, Mi-Kyung, Yun, Jong Won, Choe, Suck-Young, Lee, Jee Hye, Joe, Yeonsoo, Choi, Hye-Seon, Back, Sung Hoon, Chung, Hun Taeg, Yu, Rina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.06.2017; MDPI
• Subjects: Animals; Cell activation; Cell Culture Techniques; Cell Line; Central nervous system; Complications; Conditioning; Culture Media, Conditioned; Cytokines; Diet, High-Fat - adverse effects; Dietary Fats - administration & dosage; Dietary Fats - adverse effects; Energy balance; Gene Expression Regulation - drug effects; Heme; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; High fat diet; Homeostasis; Hypothalamus; Hypothalamus - pathology; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Interleukin 6; Macrophages; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metabolism; Mice; Microglia; Microglia - drug effects; Monocyte chemoattractant protein; Monocytes; Neurological diseases; Nitric oxide; Obesity; Obesity - chemically induced; Obesity - complications; Oxidative stress; Oxygenase; Palmitic acid; Proteins; Quercetin; Quercetin - pharmacology; Random Allocation; Rodents; quercetin; inflammation; microglia; hypothalamus; obesity
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu9070650

Obesity-induced hypothalamic inflammation is characterized by activation of microglia, which are resident macrophages of the central nervous system, and is implicated in the derangement of energy homeostasis, metabolic complications, and neurodegenerative diseases. Quercetin, a naturally occurring flavonoid, is known to protect against oxidative stress and inflammation-related metabolic complications. Here, we demonstrate that quercetin reduces obesity-induced hypothalamic inflammation by inhibiting microglia-mediated inflammatory responses, and the beneficial action of quercetin is associated with heme oxygenase (HO-1) induction. Quercetin markedly reduced the production of inflammatory mediators (monocyte chemoattractant protein (MCP)-1, interleukin (IL-6), IL-1β, nitric oxide) by microglia stimulated with saturated fatty acid palmitate and/or lipid-laden microglia-conditioned medium. Quercetin also upregulated the expression of HO-1 in palmitate-treated lipid-laden microglia, and the actions of quercetin against microglia activation accompanied by IκBα degradation were abolished by a HO-1 inhibitor. Moreover, quercetin supplementation reduced the levels of inflammatory cytokines and microglia activation markers in the hypothalamus of high fat diet (HFD)-fed obese mice, which was accompanied by upregulation of HO-1. These findings indicate that quercetin suppresses microglia-mediated inflammatory responses via the induction of HO-1, and hence protects against obesity-induced hypothalamic inflammation.