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Nat Commun. 2015 Jan 7;6:5949. doi: 10.1038/ncomms6949.

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

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MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Korea.
Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
Department of Pathology, The Fourth Military Medical University, Xi'an 710032, China.
1] Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan [2] Division of Metabolism and Endocrinology, Department of Internal Medicine, Chibune General Hospital, Osaka 555-0001, Japan.
Department of Experimental and Clinical Medicine-Obesity Center, United Hospitals-University of Ancona, Ancona 60020, Italy.
1] Department of Pediatrics and Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid E-28009, Spain [2] Instituto de Investigación La Princesa, Madrid E-28009, Spain [3] Department of Pediatrics, Universidad Autónoma de Madrid, Madrid E-28009, Spain [4] CIBER Fisiopatología de la obesidad y nutrición, Instituto de Salud Carlos III, Madrid E-28009, Spain.
Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing 210009, China.
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, Beijing 100084, China.
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
1] Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Korea [2] Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 405-760, Korea.
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge CB2 0QQ, UK.


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.

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