Cidea is associated with lipid droplets and insulin sensitivity in humans.
Storage of energy as triglyceride in large adipose-specific lipid droplets is a fundamental need in all mammals. Efficient sequestration of fat in adipocytes also prevents fatty acid overload in skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be a mitochondrial protein, colocalizes around lipid droplets with perilipin, a regulator of lipolysis. Cidea-GFP greatly enhances lipid droplet size when ectopically expressed in preadipocytes or COS cells. These results explain previous findings showing that depletion of Cidea with RNAi markedly elevates lipolysis in human adipocytes. Like perilipin, Cidea and the related lipid droplet protein Cidec/FSP27 are controlled by peroxisome proliferator-activated receptor gamma (PPARgamma). Treatment of lean or obese mice with the PPARgamma agonist rosiglitazone markedly up-regulates Cidea expression in white adipose tissue (WAT), increasing lipid deposition. Strikingly, in both omental and s.c. WAT from BMI-matched obese humans, expression of Cidea, Cidec/FSP27, and perilipin correlates positively with insulin sensitivity (HOMA-IR index). Thus, Cidea and other lipid droplet proteins define a novel, highly regulated pathway of triglyceride deposition in human WAT. The data support a model whereby failure of this pathway results in ectopic lipid accumulation, insulin resistance, and its associated comorbidities in humans.
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
Vishwajeet
V
Puri
Srijana
S
Ranjit
Silvana
S
Konda
Sarah M C
SM
Nicoloro
Juerg
J
Straubhaar
Anil
A
Chawla
My
M
Chouinard
Chenyi
C
Lin
Alison
A
Burkart
Silvia
S
Corvera
Richard A
RA
Perugini
Michael P
MP
Czech
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015992:Body Mass Index; D002352:Carrier Proteins; D006801:Humans; D007333:Insulin Resistance; D008066:Lipolysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009765:Obesity / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C502539:CIDEA protein, human; D002352:Carrier Proteins; C112510:Cidea protein, mouse; D047495:PPAR gamma; D000070778:Perilipin-1; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D045162:Thiazolidinediones; D014280:Triglycerides; C525805:fat-specific protein 27, mouse; D000077154:Rosiglitazone