| 2008 |
FSP27/CIDEC localizes to lipid droplets in white adipocytes; ablation in mice causes multilocular lipid droplets, increased lipolysis, and decreased triacylglycerol storage. Expression of FSP27 in COS cells promoted large lipid droplet formation, demonstrating a direct role in unilocular lipid droplet formation and triglyceride storage. |
FSP27 knockout mice, siRNA depletion in cultured adipocytes, ectopic expression in COS cells, lipid droplet morphology and lipolysis assays |
The Journal of clinical investigation |
High |
18654663
|
| 2008 |
Fsp27/CIDEC is a direct transcriptional target of PPARγ in liver; forced expression in hepatocytes increases triglyceride levels and lipid droplet formation, while shRNA knockdown reduces hepatic triglyceride accumulation. |
Adenoviral overexpression and shRNA knockdown in hepatocytes in vitro and in vivo; functional PPRE identified in Fsp27 promoter; ChIP and reporter assays |
Cell metabolism |
High |
18396136
|
| 2008 |
Fsp27 deficiency in mice causes upregulation of BAT-specific genes (FoxC2, PPARα, PGC1α), increased mitochondrial activity and size in WAT, and a 'browning' of white adipose tissue phenotype, indicating Fsp27 acts as a regulator of WAT identity and mitochondrial activity. |
Fsp27−/− and Fsp27/lep double-knockout mice; MEF differentiation in vitro; mitochondrial protein and gene expression analysis |
PloS one |
High |
18682832
|
| 2008 |
PPARγ2 transcriptionally activates Cidec by binding to a PPRE at the −219/−207 region of the Cidec promoter during adipogenesis. |
ChIP assay, reporter (luciferase) assay, gel shift assay, site-directed mutagenesis of PPRE |
Biochemical and biophysical research communications |
High |
18845124
|
| 2008 |
FSP27 expression in adipocytes is regulated by TNF-α (downregulation) and insulin (upregulation via phosphatidylinositol 3-kinase signals). Ectopic FSP27 expression in 293T cells and preadipocytes induces apoptotic hallmarks. |
Northern blot, pharmacological inhibition (LY-294002), ectopic expression in 293T cells, detection of apoptosis markers |
American journal of physiology. Endocrinology and metabolism |
Medium |
18198355
|
| 1992 |
The FSP27 promoter confers adipocyte-specific expression; a palindromic sequence (TTCGAAA) is necessary for this specificity and is bound by C/EBP and C/EBP-like proteins from preadipocyte and adipocyte nuclear extracts. |
Reporter gene transfection, DNase I footprinting, gel shift assay with nuclear extracts |
The Journal of biological chemistry |
High |
1339452
|
| 2003 |
Human CIDE-3 (CIDEC) induces apoptosis when transfected into 293T cells, as shown by nuclear DNA fragmentation assay. Both full-length CIDE-3 and the alternatively spliced CIDE-3α isoform (lacking exon 3) retain apoptosis-inducing activity and similar subcellular localization in cytosolic corpuscles. |
DNA fragmentation assay, GFP fusion localization, RT-PCR for isoforms |
The Biochemical journal |
Medium |
12429024
|
| 2009 |
A homozygous nonsense CIDEC mutation (E186X) that disrupts the CIDE-C domain causes mislocalization of the mutant protein and failure to increase lipid droplet size in transfected cells, resulting in partial lipodystrophy with multiloculated adipocyte lipid droplets in the patient. |
Transfection of mutant and wild-type CIDEC in cells, lipid droplet size assay, patient genetic analysis |
EMBO molecular medicine |
High |
20049731
|
| 2009 |
FSP27 CIDE-C domain (amino acids 174–192) is required for lipid droplet localization. FSP27-induced apoptosis involves caspase-9 and mitochondrial cytochrome c release and also requires this 19-amino-acid region. FSP27 CIDE-C domain interacts with CIDEA, and co-expression of CIDEA reduces FSP27 protein levels. |
eGFP-FSP27 deletion constructs, lipid droplet localization assays in HeLa cells, caspase inhibitor experiments, cytochrome c release assay, co-immunoprecipitation |
American journal of physiology. Endocrinology and metabolism |
High |
19843876
|
| 2011 |
Fsp27 is focally enriched at lipid droplet–lipid droplet contact sites (LDCS). FRAP analysis demonstrates lipid exchange between contacting LDs in Fsp27-expressing but not Fsp27-deficient adipocytes. Live-cell imaging reveals directional net lipid transfer from smaller to larger LDs at LDCSs mediated by Fsp27, consistent with internal pressure differences between LD pairs. |
FRAP, live-cell imaging, Fsp27-deficient adipocytes, fluorescence microscopy of LDCS |
The Journal of cell biology |
High |
22144693
|
| 2011 |
FSP27 promotes lipid droplet clustering followed by fusion. Domain mapping shows amino acids 173–220 are necessary and sufficient for LD targeting and initial clustering; amino acids 120–140 are essential but not sufficient for LD enlargement; amino acids 120–210 are necessary and sufficient for both clustering and fusion. Triglyceride accumulation is associated with LD enlargement but not clustering alone. |
GFP-fusion deletion mutant constructs, fluorescence microscopy in adipocytes |
PloS one |
High |
22194867
|
| 2013 |
Perilipin1 (Plin1) interacts with the CIDE-N domain of Fsp27 and markedly increases Fsp27-mediated lipid exchange, lipid transfer, and lipid droplet growth. The CIDE-N domain of Fsp27 forms homodimers required for lipid exchange and transfer; disruption of CIDE-N homodimerization abolishes these activities. Plin1 can rescue the activity of CIDE-N homodimerization-defective Fsp27 mutants. |
Co-immunoprecipitation, FRAP, live-cell imaging, site-directed mutagenesis of CIDE-N homodimerization interface, RNAi depletion of Plin1 and Fsp27 |
Nature communications |
High |
23481402
|
| 2013 |
FSP27 (CIDEC) co-localizes and interacts with PLIN1 in human primary adipocytes. The C-terminal domain of FSP27 (aa 120–220) mediates interaction with PLIN1. Co-expression of FSP27 and PLIN1 increases average lipid droplet size and promotes unilocular lipid droplet formation. |
Co-immunoprecipitation, co-localization by immunofluorescence, triglyceride content assay, glycerol release assay, ectopic expression in human adipocytes |
Biochemical and biophysical research communications |
High |
23399566
|
| 2013 |
Crystal structure of the CIDE-N domain of FSP27 solved at 2.0 Å reveals a homodimeric interface similar to the CAD/ICAD heterodimer; structural homologs include the PB1 domain of BEM1P, ubiquitin-like domain of BAG6, and ubiquitin. |
X-ray crystallography at 2.0 Å resolution |
Biochemical and biophysical research communications |
High |
24025675
|
| 2014 |
FSP27 (aa 120–220) interacts with ATGL in human adipocytes to inhibit its lipolytic function and promote triglyceride storage. FSP27 depletion increases lipolysis and impairs insulin signaling (decreased AKT phosphorylation); reducing lipolysis by ATGL depletion or FSP27 overexpression protects against free fatty acid-induced insulin resistance. |
Co-immunoprecipitation, siRNA knockdown of FSP27 and ATGL, ATGL KO mouse-derived fibroblasts, lipolysis assays, AKT phosphorylation |
The Journal of biological chemistry |
High |
24627478
|
| 2014 |
AMPK activation (by AICAR or phenformin) induces ubiquitination and proteasomal degradation of FSP27 in adipocytes, leading to multilocularization of lipid droplets. HSC70 is identified as a binding partner of FSP27 that stabilizes it; HSC70 knockdown reduces FSP27 half-life. |
Co-immunoprecipitation, mass spectrometry, siRNA knockdown, cycloheximide chase assay, AICAR/phenformin treatment, ubiquitination assay |
American journal of physiology. Endocrinology and metabolism |
High |
25315694
|
| 2015 |
CREBH (liver-enriched transcription factor) directly activates the Fsp27β promoter (but not the Fsp27α/PPARγ-driven promoter) in hepatocytes. Fsp27β localizes to lipid droplet surfaces and suppresses lipolysis; its enforced expression promotes lipid droplet enlargement and hepatic TG accumulation. |
Promoter reporter assays, constitutively active CREBH overexpression, CREBH KO fasted mice, lipid droplet imaging, lipolysis assays |
Hepatology (Baltimore, Md.) |
High |
25125366
|
| 2015 |
CIDEC/FSP27 is a direct transcriptional target of PPARα in mouse and human hepatocytes. Adenoviral silencing of hepatic Fsp27 abolishes fasting-induced liver steatosis. PPARα agonist (fenofibrate) and Fsp27 ASO synergize to reduce hepatic TG accumulation. |
ChIP, promoter reporter assay, adenoviral shRNA in vivo, ASO treatment, fasting model |
Hepatology (Baltimore, Md.) |
High |
25418138
|
| 2015 |
Cidec promotes adipocyte differentiation by interacting with AMPKα1 and promoting its degradation via the ubiquitin–proteasome pathway, thereby reducing AMPKα levels. |
Yeast two-hybrid, co-immunoprecipitation, immunofluorescence co-localization, RNAi knockdown, proteasome inhibitor experiments |
Biochimica et biophysica acta |
Medium |
26367078
|
| 2016 |
TNF-α downregulates CIDEC expression in human adipocytes through MEK/ERK-mediated phosphorylation of PPARγ at Ser273 and its subsequent nuclear export; inhibiting MEK/ERK prevents TNF-α-mediated CIDEC downregulation. |
MEK/ERK inhibitors, constitutively active MEK1 mutant, immunofluorescence, subcellular fractionation, reporter assay |
Obesity (Silver Spring, Md.) |
Medium |
27062372
|
| 2017 |
HDAC6 deacetylates CIDEC at lysine 56 (K56); the acetyltransferase PCAF acetylates CIDEC at K56 on the endoplasmic reticulum. Acetylation of CIDEC stabilizes it and promotes lipid droplet fusion, while HDAC6-mediated deacetylation leads to CIDEC destabilization. Fatty acids prevent CIDEC deacetylation by promoting dissociation of CIDEC from HDAC6 and increasing association with PCAF. |
Adipocyte-specific Hdac6 KO mice, Co-IP, mass spectrometry, site-directed mutagenesis at K56, lipid droplet fusion assay |
The Journal of clinical investigation |
High |
28287402
|
| 2018 |
Growth hormone (GH) reduces FSP27 expression by activating MEK/ERK, which phosphorylates PPARγ at Ser273 and causes its translocation from nucleus to cytosol, thereby reducing PPARγ transcriptional activity at the FSP27 promoter. FSP27 overexpression inhibits PPARγ Ser273 phosphorylation and promotes its nuclear retention, suppressing GH-induced lipolysis. |
MEK/ERK inhibitors, GH antagonist treatment, immunofluorescence, PPARγ Ser273 phosphorylation assay, FSP27 overexpression in human adipocytes |
American journal of physiology. Endocrinology and metabolism |
Medium |
30325658
|
| 2018 |
GH modulates FSP27 expression through both MEK/ERK- and STAT5-dependent intracellular signaling, which interact to regulate PPARγ activity on the FSP27 promoter. FSP27 overexpression fully suppresses GH-induced lipolysis and insulin resistance. |
Pathway-specific inhibitors, transgenic GH overexpression mice, FSP27 overexpression, lipolysis assays |
The Journal of endocrinology |
Medium |
30400015
|
| 2018 |
FTO promotes SREBP1c nuclear translocation and maturation, which in turn transcriptionally activates CIDEC via its promoter. CIDEC knockdown reduces SREBP1c-induced lipogenesis in HepG2 cells. |
FTO overexpression/knockdown, SREBP1c overexpression/knockdown, luciferase reporter assay for CIDEC promoter, lipogenesis assays |
Biochimica et biophysica acta. Molecular and cell biology of lipids |
Medium |
29486327
|
| 2018 |
The polybasic RKKR motif in the linker region between CIDE-N and CIDE-C domains of CIDEC interacts with acidic phospholipids via electrostatic attraction. Deletion of the linker or mutation of RKKR increases formation of supersized LDs; this enhanced LD fusion requires intact CIDE-N domain interaction. |
Targeted protein deletions and mutations, GFP expression, fluorescence microscopy, lipid droplet size quantification |
The Journal of biological chemistry |
High |
30361435
|
| 2021 |
Cidec undergoes phase separation through homomeric interactions of its multivalent N-terminus, forming gel-like condensates at LD-LD contact sites (LDCS). These condensates generate lipid-permeable fusion plates geometrically constrained by donor LDs, containing stochastic sub-compartments that represent lipid passageways during LD fusion. |
In vitro phase separation assay, live-cell imaging, super-resolution microscopy, FRAP, genetic deletion constructs |
Developmental cell |
High |
34508658
|
| 2022 |
CIDEC regulates ATGL enzymatic activity via interaction with ATGL's activator CGI-58, reducing free fatty acid release and lipotoxicity. Adipose-specific CIDEC transgenic mice (but not E186X mutant) are protected from HFD-induced glucose intolerance and show reduced serum triglycerides. |
Transgenic mouse model, transcriptomics, lipidomics, recombinant CIDEC treatment of human adipose tissue, Co-IP |
The Journal of biological chemistry |
High |
35963433
|
| 2023 |
Electron cryo-tomography reveals that Cidec facilitates lipid transfer through closely apposed LD monolayers at LD-LD interfaces. Transfer is slowed by increasing the distance between monolayers and follows exponential kinetics, consistent with pressure-driven transfer through 'leaky' monolayers. |
Electron cryo-tomography, quantitative live fluorescence microscopy of lipid transfer kinetics |
Cell reports |
High |
36800289
|
| 2023 |
Paxillin family proteins Hic-5 and LPXN bind CIDEC, reduce its ubiquitination, and inhibit its proteasomal degradation, thereby increasing CIDEC protein levels and promoting lipid droplet enlargement and lipid storage in adipocytes. |
HTRF-based high-throughput screening, Co-IP, siRNA knockdown, proteasome inhibitor experiments, lipid droplet imaging |
The Journal of biological chemistry |
Medium |
38159847
|
| 2016 |
FSP27 negatively regulates acidic residues (D215, E218, E219, E220) in the polar carboxy-terminal region (aa 202–239) of FSP27 are essential for LD enlargement; the amino-terminal domain (aa 1–130) is dispensable but accelerates LD growth. The C-terminal domain (aa 131–239) is required for LD expansion. |
Deletion and charge-reversal mutagenesis of FSP27 domains, LD morphology assay |
FEBS letters |
Medium |
26921608
|
| 2011 |
Loss of MKP-1 inhibits PPARγ function by increasing MAPK-dependent phosphorylation at inhibitory serine 112, thereby repressing Fsp27 expression and reducing PPARγ-induced lipid droplet formation in hepatocytes. |
MKP-1 KO mice (db/db background), microarray, PPARγ phosphorylation assay, hepatocyte lipid droplet formation assay |
The Journal of biological chemistry |
Medium |
21521693
|
| 2010 |
Insulin increases CIDEC mRNA and protein in human adipocytes, leading to enlargement of lipid droplets; depletion of CIDEC (but not CIDEA) by siRNA abolishes insulin-induced lipid droplet enlargement and significantly increases glycerol release (lipolysis). |
siRNA knockdown of CIDEC and CIDEA, lipid droplet size measurement, glycerol release assay, insulin treatment |
Journal of lipid research |
High |
20154362
|
| 2011 |
Insulin upregulates CIDEC expression via PI3K/JNK2 (not JNK1, MEK, or p38) signaling in human adipocytes. siRNA-mediated depletion of JNK2, but not JNK1, inhibits insulin-induced CIDEC upregulation and lipid droplet enlargement. |
PI3K, Akt, JNK, MEK, p38 inhibitors; selective JNK1/2 siRNA knockdown; lipid droplet imaging |
Journal of lipid research |
Medium |
21636835
|
| 2010 |
CIDE-3 (CIDEC) interacts with LITAF (lipopolysaccharide-induced tumor necrosis factor) in hepatic cells, as identified by yeast two-hybrid screening; overexpression of CIDE-3 induces apoptosis in HCC cells. |
Yeast two-hybrid, ectopic overexpression, flow cytometry apoptosis assay |
Medical oncology (Northwood, London, England) |
Low |
20957525
|
| 2014 |
CIDEC translocates from the ER to lipid droplets upon fatty acid stimulation. The N-domain (aa 1–173) is involved in LD localization; the C-domain (aa 174–238) is necessary for LD fusion; the 106–173 aa region serves as an ER-binding domain. |
Ectopic expression of CIDEC domain mutants in HepG2 cells, fluorescence microscopy, fatty acid stimulation |
Genes to cells : devoted to molecular & cellular mechanisms |
Medium |
25255829
|
| 2022 |
CIDEC interacts with 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT) in intestinal cells to accelerate phosphatidic acid synthesis and promote TG accumulation. Small intestine-specific CIDEC knockout mice on HFD have lower body fat, liver TG, and higher fecal TG than wild-type. |
Small intestine-specific Cre/LoxP CIDEC KO mice, Co-IP with AGPAT, lipid/metabolic phenotyping |
International journal of biological sciences |
Medium |
36263170
|
| 2023 |
Endothelial CIDEC interacts with VEGFA-VEGFR2 signaling to reduce VEGFA and VEGFR2 degradation, thereby increasing VEGFR2 activation and improving angiogenesis and insulin signaling in endothelial cells. |
Endothelial-specific CIDEC transgenic mice, endothelial VEGFR2 activation assays, HFD metabolic phenotyping, vascular relaxation assays |
Diabetes |
Medium |
36256836
|
| 2015 |
FSP27/CIDEC promotes alcoholic steatohepatitis: chronic-plus-binge ethanol feeding upregulates Fsp27 via PPARγ (for Fsp27α) and CREBH (for Fsp27β); hepatocyte-specific Fsp27 KO or adenoviral Fsp27 shRNA markedly reduces ASH. FSP27 overexpression and ethanol synergistically increase mitochondrial reactive oxygen species and hepatocyte damage. |
Hepatocyte-specific Fsp27 KO mice (Fsp27Hep−/−), adenoviral shRNA, PPARγ inhibitor (GW9662), mitochondrial ROS assay, ethanol feeding model |
Gastroenterology |
High |
26099526
|
| 2024 |
FSP27 deficiency in adipocytes reduces CCL2 expression and secretion through a JNK-dependent pathway, thereby reducing macrophage migration and PVAT inflammation in obesity-associated abdominal aortic aneurysm. Cidec overexpression rescues CCL2 secretion after Fsp27 knockdown. |
Global and adipose-specific FSP27 KO mice, 3T3-L1 adipocyte knockdown/overexpression, CCL2 ELISA, macrophage migration assay, JNK inhibition |
Life metabolism |
Medium |
39872985
|
| 2025 |
CIDEC depletion after peak LD accumulation in regenerating liver promotes TG mobilization via fatty acid oxidation (FAO), supporting liver regeneration. CIDEC overexpression or DGAT2 overexpression exacerbates TG retention and impairs regeneration. FAO inhibition abolishes the pro-regenerative effect of CIDEC depletion. |
CIDEC KO and overexpression in mice, DGAT2 overexpression, FAO inhibitor (etomoxir), lipidomics, transcriptomics, partial hepatectomy model |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
High |
41255220
|