Chronic exposure to high fat diet triggers myelin disruption and interleukin-33 upregulation in hypothalamus

Hui Ting Huang, Sheng Feng Tsai, Hung Tsung Wu, Hsin Ying Huang, Han Hsueh Hsieh, Yu Ming Kuo, Po See Chen, Chung Shi Yang, Shun Fen Tzeng

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Background: Hypothalamic inflammation including astrogliosis and microglia activation occurs after intake of high fat diet (HFD) in rodent models or in obese individuals. However, the effect of chronic HFD feeding on oligodendrocytes (OLGs), a myelin-producing glial population in the central nervous system (CNS), remains unclear. In this study, we used 8-week old male C57BL/6 mice fed by HFD for 3-6 months to induce chronic obesity. Results: The transmission electron microscopy imaging analysis showed that the integrity of hypothalamic myelin was disrupted after HFD feeding for 4 and 6 months. Moreover, the accumulation of Iba1+-microglia with an amoeboid hypertrophic form was continually observed in arcuate nucleus of HFD-fed mice during the entire feeding time period. Interleukin-33 (IL-33), a tissue alarmin upon injury to the CNS, was detected with an increased level in hypothalamus after HFD feeding for 3 and 4 months. Furthermore, the in vitro study indicated that exposure of mature OLGs to IL-33 impaired OLG cell structure along with a decline in the expression of myelin basic protein. Conclusions: Altogether, our findings demonstrate that chronic HFD feeding triggers hypothalamic myelin disruption in accompany with IL-33 upregulation and prolonged microglial activation in hypothalamus. Given that the addition of exogenous IL-33 was harmful for the maturation of OLGs, an increase in IL-33 by chronic HFD feeding might contribute to the induction of hypothalamic myelin disruption.

Original languageEnglish
Article number33
JournalBMC Neuroscience
Issue number1
Publication statusPublished - Jul 10 2019
Externally publishedYes


  • Glia
  • IL-33
  • Microglia
  • Myelin
  • Obesity
  • Oligodendrocytes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience


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