https://scholars.lib.ntu.edu.tw/handle/123456789/577940
標題: | Apolipoprotein E deficiency activates thermogenesis of white adipose tissues in mice through enhancing β-hydroxybutyrate production from precursor cells | 作者: | Jiang, Chung Lin Chen, Ying Fang FU-JUNG LIN |
關鍵字: | apolipoprotein E | browning | white adipose tissue | β-hydroxybutyrate | 公開日期: | 1-八月-2021 | 出版社: | Federation of American Societies for Experimental Biology | 卷: | 35 | 期: | 8 | 起(迄)頁: | e21760 | 來源出版物: | FASEB Journal | 摘要: | White adipose tissue (WAT) has the capacity to undergo a white-to-beige phenotypic switch, known as browning, in response to stimuli such as cold. However, the mechanism underlying beige adipocyte formation is largely unknown. Apolipoprotein E (ApoE) is highly induced in WAT and has been implicated in lipid metabolism. Here, we show that ApoE deficiency in mice increased oxygen consumption and thermogenesis and enhanced adipose browning pattern in inguinal WAT (iWAT), with associated characteristics such as increased Ucp1 and Pparγ expression. At the cellular level, ApoE deficient beige adipocytes had increased glucose uptake and higher mitochondrial respiration than wild-type cells. Mechanistically, we showed that ApoE deficient iWAT and primary adipose precursor cells activated the thermogenic genes program by stimulating the production of ketone body β-hydroxybutyrate (βHB), a novel adipose browning promoting factor. This was accompanied by increased expression of genes involved in ketogenesis and could be compromised by the treatment for ketogenesis inhibitors. Consistently, ApoE deficient mice show higher serum βHB level than wild-type mice in the fed state and during cold exposure. Our results further demonstrate that the increased βHB production in ApoE deficient adipose precursor cells could be attributed, at least in part, to enhanced Cd36 expression and CD36-mediated fatty acid utilization. Our findings uncover a previously uncharacterized role for ApoE in energy homeostasis via its cell-autonomous action in WAT. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/577940 | ISSN: | 08926638 | DOI: | 10.1096/fj.202100298RR |
顯示於: | 生化科技學系 |
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