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

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, Lizhen Wu, Shenghong Ju, Feifei Guan, Hongyuan Yang, Cheol Soo Choi (), David B. Savage () and Peng Li ()
Additional contact information
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
Cristina M. Zingaretti: United Hospitals-University of Ancona
Saverio Cinti: United Hospitals-University of Ancona
Jesús Argente: Hospital Infantil Universitario Niño Jesús
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
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

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms6949

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