title: Uric Acid Produces an Inflammatory Response through Activation of NF-κB in the Hypothalamus: Implications for the Pathogenesis of Metabolic Disorders.
abstract: Epidemiological studies have shown that an elevated uric acid (UA) level predicts the development of metabolic syndrome and diabetes; however, there is no direct evidence of this, and the underlying mechanism remains unclear. Here, we showed that a high-UA diet triggered the expression of pro-inflammatory cytokines, activated the NF-κB pathway, and increased gliosis in the hypothalamus. Intracerebroventricular injection of UA induced hypothalamic inflammation and reactive gliosis, whereas these effects were markedly ameliorated by the inhibition of NF-κB. Moreover, magnetic resonance imaging confirmed that hyperuricemia in rodents and humans was associated with gliosis in the mediobasal hypothalamus. Importantly, the rats administered UA exhibited dyslipidemia and glucose intolerance, which were probably mediated by hypothalamic inflammation and hypothalamic neuroendocrine alterations. These results suggest that UA can cause hypothalamic inflammation via NF-κB signaling. Our findings provide a potential therapeutic strategy for UA-induced metabolic disorders.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Anhui Medical University, Hefei 230032, China.
authors.forename: Youzhi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Shao
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Fabao
authors.initials: F
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Zeping
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Shao
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Liangxue
authors.initials: L
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier; D050171:Dyslipidemias / Q000097:blood / Q000209:etiology*; D005911:Gliosis / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014527:Uric Acid / Q000097:blood / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016328:NF-kappa B; D014527:Uric Acid