Uric Acid Produces an Inflammatory Response through Activation of NF-κB in the Hypothalamus: Implications for the Pathogenesis of Metabolic Disorders

Sci Rep. 2015 Jul 16;5:12144. doi: 10.1038/srep12144.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Blood-Brain Barrier
  • Dyslipidemias / blood
  • Dyslipidemias / etiology*
  • Gliosis / metabolism
  • Glucose Tolerance Test*
  • Humans
  • Hypothalamus / metabolism*
  • Hypothalamus / pathology
  • Inflammation / etiology*
  • Magnetic Resonance Imaging
  • Male
  • NF-kappa B / metabolism*
  • Rats
  • Rats, Wistar
  • Uric Acid / blood
  • Uric Acid / metabolism*

Substances

  • Biomarkers
  • NF-kappa B
  • Uric Acid