TY - JOUR
T1 - Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC
AU - Rubio-Cabezas, Oscar
AU - Puri, Vishwajeet
AU - Murano, Incoronata
AU - Saudek, Vladimir
AU - Semple, Robert K.
AU - Dash, Satya
AU - Hyden, Caroline S S
AU - Bottomley, William
AU - Vigouroux, Corinne
AU - Magré, Jocelyne
AU - Raymond-Barker, Philippa
AU - Murgatroyd, Peter R.
AU - Chawla, Anil
AU - Skepper, Jeremy N.
AU - Chatterjee, V. Krishna
AU - Suliman, Sara
AU - Consortium, LD Screening
AU - Patch, Ann Marie
AU - Agarwal, Anil K.
AU - Garg, Abhimanyu
AU - Barroso, Inês
AU - Cinti, Saverio
AU - Czech, Michael P.
AU - Argente, Jesús
AU - O'Rahilly, Stephen
AU - Savage, David B.
PY - 2009/8
Y1 - 2009/8
N2 - 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. 2009 EMBO Molecular Medicine.
AB - 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. 2009 EMBO Molecular Medicine.
KW - CIDEC (Fsp27)
KW - Insulin resistance
KW - Lipid droplet
KW - Lipodystrophy
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U2 - 10.1002/emmm.200900037
DO - 10.1002/emmm.200900037
M3 - Article
C2 - 20049731
AN - SCOPUS:70450220107
SN - 1757-4676
VL - 1
SP - 280
EP - 287
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 5
ER -