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

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.

• Authors: Jihyeon Yang, Chu-Sook Kim, Thai Hien Tu, Min-Seon Kim, Tsuyoshi Goto, Teruo Kawada, Myung-Sook Choi, Taesun Park, Mi-Kyung Sung, Jong Won Yun, Suck-Young Choe, Jee Hye Lee, Yeonsoo Joe, Hye-Seon Choi, Sung Hoon Back, Hun Taeg Chung, Rina Yu
• Journal: Nutrients (Nutrients) Vol. 9 Issue 7 (Jun 23 2017) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 28644409 (Publication Type: Journal Article)

Chemical References

• Culture Media, Conditioned
• Dietary Fats
• Membrane Proteins
• Quercetin
• Heme Oxygenase-1
• Hmox1 protein, mouse

Topics

• Animals
• Cell Culture Techniques
• Cell Line
• Culture Media, Conditioned
• Diet, High-Fat (adverse effects)
• Dietary Fats (administration & dosage, adverse effects)
• Gene Expression Regulation (drug effects)
• Heme Oxygenase-1 (genetics, metabolism)
• Hypothalamus (pathology)
• Inflammation (chemically induced, drug therapy)
• Male
• Membrane Proteins (genetics, metabolism)
• Mice
• Microglia (drug effects)
• Obesity (chemically induced, complications)
• Quercetin (pharmacology)
• Random Allocation