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

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

doi:10.1186/s12868-019-0516-6

Abstract

BackgroundHypothalamic 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.ResultsThe 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.ConclusionsAltogether, 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.

Highlights

Hypothalamic inflammation including astrogliosis and microglia activation occurs after intake of high fat diet (HFD) in rodent models or in obese individuals
In conjunction with our in vitro study that exposure of mature oligoden‐ drocyte (OLG) to IL-33 induced the injury of OLG morphology, the findings suggest that impaired myelin microstructure in hypothalamus after HFD feeding might be caused in part by the action of IL-33 molecules increased by chronic HFD feeding
The levels of myelin basic protein (MBP) protein isoforms (14–21.5 kDa) in hypothalamus were not altered by HFD feeding, myelin proteolipid protein (PLP) levels in hypothalamus were moderately increased after HFD feeding for 4 months when compared to that measured in Chow-fed mice (Fig. 1b)

Summary

Introduction

Hypothalamic inflammation including astrogliosis and microglia activation occurs after intake of high fat diet (HFD) in rodent models or in obese individuals. The effect of chronic HFD feeding on oligodendro‐ cytes (OLGs), a myelin-producing glial population in the central nervous system (CNS), remains unclear. Hypothalamic inflammation occurs in genetic modified animal models of obesity or high fat diet (HFD)-fed animals [5, 8,9,10]. The activation of microglia and astrocytes, referred as gliosis, has been known to play a critical role in the regulation of HFD-induced resistance to leptin and insulin in company with the disturbance of energy homeostasis [11,12,13,14]. The loss of oligodendrocytes (OLGs), a myelin-producing glial population in the

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