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Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice

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  • Linkang Zhou

    (MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Shi-Young Park

    (Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University)

  • Li Xu

    (Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences)

  • Xiayu Xia

    (MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Jing Ye

    (The Fourth Military Medical University)

  • Lu Su

    (MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Kyeong-Hoon Jeong

    (Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University)

  • Jang Ho Hur

    (Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University)

  • Hyunhee Oh

    (Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University)

  • Yoshikazu Tamori

    (Kobe University Graduate School of Medicine
    Chibune General Hospital)

  • Cristina M. Zingaretti

    (United Hospitals-University of Ancona)

  • Saverio Cinti

    (United Hospitals-University of Ancona)

  • Jesús Argente

    (Hospital Infantil Universitario Niño Jesús
    Instituto de Investigación La Princesa
    Universidad Autónoma de Madrid
    CIBER Fisiopatología de la obesidad y nutrición, Instituto de Salud Carlos III)

  • Miao Yu

    (MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Lizhen Wu

    (MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Shenghong Ju

    (Jiangsu Key Laboratory of Molecular and Functional Imaging, Zhongda Hospital, Southeast University)

  • Feifei Guan

    (Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College)

  • Hongyuan Yang

    (School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia)

  • Cheol Soo Choi

    (Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University
    Gachon University Gil Medical Center)

  • David B. Savage

    (University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science)

  • Peng Li

    (MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University)

Abstract

Fsp27 is a lipid droplet-associated protein almost exclusively expressed in adipocytes where it facilitates unilocular lipid droplet formation. In mice, Fsp27 deficiency is associated with increased basal lipolysis, ‘browning’ of white fat and a healthy metabolic profile, whereas a patient with congenital CIDEC deficiency manifested an adverse lipodystrophic phenotype. Here we reconcile these data by showing that exposing Fsp27-null mice to a substantial energetic stress by crossing them with ob/ob mice or BATless mice, or feeding them a high-fat diet, results in hepatic steatosis and insulin resistance. We also observe a striking reduction in adipose inflammation and increase in adiponectin levels in all three models. This appears to reflect reduced activation of the inflammasome and less adipocyte death. These findings highlight the importance of Fsp27 in facilitating optimal energy storage in adipocytes and represent a rare example where adipose inflammation and hepatic insulin resistance are disassociated.

Suggested Citation

  • Linkang Zhou & Shi-Young Park & Li Xu & Xiayu Xia & Jing Ye & Lu Su & Kyeong-Hoon Jeong & Jang Ho Hur & Hyunhee Oh & Yoshikazu Tamori & Cristina M. Zingaretti & Saverio Cinti & Jesús Argente & Miao Yu, 2015. "Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6949
    DOI: 10.1038/ncomms6949
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    Cited by:

    1. Xinyan Zhou & Mengchao Yu & Luzhen Ma & Jinyu Fu & Jingwei Guo & Jieqiong Lei & Zheng Fu & Yong Fu & Qipeng Zhang & Chen-Yu Zhang & Xi Chen, 2022. "In vivo self-assembled siRNA as a modality for combination therapy of ulcerative colitis," Nature Communications, Nature, vol. 13(1), pages 1-23, December.

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