1. Quercetin Protects Obesity-Induced Hypothalamic Inflammation by Reducing Microglia-Mediated Inflammatory Responses via HO-1 Induction.
- Author
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Yang J, Kim CS, Tu TH, Kim MS, Goto T, Kawada T, Choi MS, Park T, Sung MK, Yun JW, Choe SY, Lee JH, Joe Y, Choi HS, Back SH, Chung HT, and Yu R
- Subjects
- Animals, Cell Culture Techniques, Cell Line, Culture Media, Conditioned, Diet, High-Fat adverse effects, Dietary Fats administration & dosage, Dietary Fats adverse effects, Gene Expression Regulation drug effects, Heme Oxygenase-1 genetics, Inflammation drug therapy, Male, Membrane Proteins genetics, Mice, Obesity chemically induced, Random Allocation, Heme Oxygenase-1 metabolism, Hypothalamus pathology, Inflammation chemically induced, Membrane Proteins metabolism, Microglia drug effects, Obesity complications, Quercetin pharmacology
- Abstract
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.
- Published
- 2017
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