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Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC

  1. Oscar Rubio-Cabezas1,14,15,†,
  2. Vishwajeet Puri2,†,
  3. Incoronata Murano3,
  4. Vladimir Saudek4,
  5. Robert K. Semple4,
  6. Satya Dash4,
  7. Caroline S. S. Hyden4,
  8. William Bottomley5,
  9. Corinne Vigouroux6,7,8,
  10. Jocelyne Magré6,7,
  11. Philippa Raymond-Barker9,
  12. Peter R. Murgatroyd9,
  13. Anil Chawla2,
  14. Jeremy N. Skepper10,
  15. V. Krishna Chatterjee4,
  16. Sara Suliman11,
  17. Ann-Marie Patch12,
  18. Anil K. Agarwal13,
  19. Abhimanyu Garg13,
  20. Inês Barroso5,
  21. Saverio Cinti3,
  22. Michael P. Czech2,
  23. Jesús Argente1,14,15,
  24. Stephen O'Rahilly4,
  25. David B. Savage4,*

Article first published online: 5 AUG 2009

DOI: 10.1002/emmm.200900037

Issue

EMBO Molecular Medicine

EMBO Molecular Medicine

Volume 1, Issue 5, pages 280–287, August 2009

Additional Information

How to Cite

Rubio-Cabezas, O., Puri, V., Murano, I., Saudek, V., Semple, R. K., Dash, S., Hyden, C. S. S., Bottomley, W., Vigouroux, C., Magré, J., Raymond-Barker, P., Murgatroyd, P. R., Chawla, A., Skepper, J. N., Chatterjee, V. K., Suliman, S., Patch, A.-M., Agarwal, A. K., Garg, A., Barroso, I., Cinti, S., Czech, M. P., Argente, J., O'Rahilly, S. and Savage, D. B. (2009), Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. EMBO Molecular Medicine, 1: 280–287. doi: 10.1002/emmm.200900037

Author Information

  1. 1

    Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain

  2. 2

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA

  3. 3

    Institute of Normal Human Morphology, University of Ancona, Ancona, Italy

  4. 4

    Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

  5. 5

    Metabolic Disease Group, The Wellcome Trust Sanger Institute, Hinxton, UK

  6. 6

    UPMC Univ Paris 06, UMR_S938, Paris, France

  7. 7

    INSERM, UMR_S938, Faculté de Médecine Pierre et Marie Curie, Site Saint-Antoine, Paris, France

  8. 8

    AP-HP, Hôpital Tenon, Service de Biochimie et Hormonologie, Paris, France

  9. 9

    Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital, Cambridge, UK

  10. 10

    Multi-imaging Centre, Physiology Development & Neuroscience, University of Cambridge, Cambridge, UK

  11. 11

    Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Oxford, UK

  12. 12

    Institute of Biomedical and Clinical Science (AM.P.), Peninsula Medical School, Exeter, UK

  13. 13

    Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

  14. 14

    Department of Pediatrics, Universidad Autónoma de Madrid; Madrid, Spain

  15. 15

    CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain

  1. †

    These authors contributed equally to this work.

*Tel: +44 1223 767923; Fax: +44 1223 330598

Publication History

  1. Issue published online: 5 AUG 2009
  2. Article first published online: 5 AUG 2009
  3. Manuscript Accepted: 2 JUL 2009
  4. Manuscript Revised: 29 JUN 2009
  5. Manuscript Received: 14 APR 2009

Funded by

  • Wellcome Trust (R.K.S., V.K.K.C., S.O'R., D.B.S., W.B., I.B.(WT)). Grant Number: 077016/Z/05/Z
  • CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) from the ‘Instituto de Salud Carlos III’
  • Fundación Endocrinología y Nutrición, Madrid, Spain (J.A.)
  • GlaxoSmithKline (D.B.S.)
  • U.K. NIHR Cambridge Biomedical Research Centre
  • National Institutes of Health. Grant Numbers: DK30898, DK60837, DK54387
  • Biomedical Imaging Core Facility of the University of Massachusetts Diabetes and Endocrinology Center (National Institutes of Health). Grant Number: DK32520
  • Diabetes UK (S.S.)
  • Italian Ministry of University. Grant Number: FIRB RBIN047PZY_000
  • Cofin. PRIN bando 2007
  • Aide aux Jeunes Diabétiques (AJD)
  • Association de Langue Française pour l'Etude du Diabète et des Maladies Métaboliques (ALFEDIAM)
  • French National Institute for Health and Medical Research (INSERM)

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Keywords:

  • lipodystrophy;
  • insulin resistance;
  • lipid droplet;
  • CIDEC (Fsp27)

Abstract

Lipodystrophic syndromes are characterized by adipose tissue deficiency. Although rare, they are of considerable interest as they, like obesity, typically lead to ectopic lipid accumulation, dyslipidaemia and insulin resistant diabetes. In this paper we describe a female patient with partial lipodystrophy (affecting limb, femorogluteal and subcutaneous abdominal fat), white adipocytes with multiloculated lipid droplets and insulin-resistant diabetes, who was found to be homozygous for a premature truncation mutation in the lipid droplet protein cell death-inducing Dffa-like effector C (CIDEC) (E186X). The truncation disrupts the highly conserved CIDE-C domain and the mutant protein is mistargeted and fails to increase the lipid droplet size in transfected cells. In mice, Cidec deficiency also reduces fat mass and induces the formation of white adipocytes with multilocular lipid droplets, but in contrast to our patient, Cidec null mice are protected against diet-induced obesity and insulin resistance. In addition to describing a novel autosomal recessive form of familial partial lipodystrophy, these observations also suggest that CIDEC is required for unilocular lipid droplet formation and optimal energy storage in human fat.

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