| 2008 |
FSP27/CIDEC localizes to lipid droplets in white adipocytes and promotes formation of unilocular lipid droplets; ablation results in multilocular lipid droplets, increased lipolysis, decreased triacylglycerol storage, and increased mitochondrial biogenesis in white adipose tissue. |
FSP27 knockout mice, siRNA depletion in cultured adipocytes, ectopic expression in COS cells, in vivo phenotypic analysis |
The Journal of clinical investigation |
High |
18654663
|
| 2011 |
Fsp27 is focally enriched at the lipid droplet-lipid droplet contact site (LDCS) and mediates directional net lipid transfer from smaller to larger LDs, driving LD growth via a pressure-difference mechanism. |
Live-cell imaging, FRAP/photobleaching, Fsp27-deficient adipocytes, Fsp27-overexpressing cells, biophysical analysis of LD internal pressure |
The Journal of cell biology |
High |
22144693
|
| 2013 |
Perilipin1 (Plin1) interacts with the CIDE-N domain of Fsp27 and markedly increases Fsp27-mediated lipid exchange, lipid transfer, and lipid droplet growth; CIDE-N homodimerization is required for Fsp27 activity and Plin1 can restore activity of CIDE-N homodimerization-defective mutants. |
Co-immunoprecipitation, FRAP, live-cell imaging, domain mutagenesis, siRNA depletion |
Nature communications |
High |
23481402
|
| 2013 |
Human FSP27 (CIDEC) interacts with PLIN1 via its C-terminal domain (aa 120–220) in primary human adipocytes, and co-expression of FSP27 and PLIN1 increases average lipid droplet size and promotes unilocular adipocyte formation. |
Co-localization by immunofluorescence, co-immunoprecipitation, deletion mapping, triglyceride/glycerol assays in human adipocytes |
Biochemical and biophysical research communications |
Medium |
23399566
|
| 2009 |
A truncation mutation in the CIDE-C domain of human CIDEC (E186X) causes partial lipodystrophy with multilocular lipid droplets; the mutant protein is mistargeted and fails to increase lipid droplet size in transfected cells, establishing the CIDE-C domain as necessary for LD targeting and function. |
Human genetics (homozygous truncation mutation), transfection of mutant vs. WT CIDEC in cells, lipid droplet size assay |
EMBO molecular medicine |
High |
20049731
|
| 2011 |
FSP27 promotes LD clustering (requiring aa 173–220) followed by their fusion into enlarged droplets (requiring aa 120–210), with LD enlargement—but not clustering—associated with triglyceride accumulation. |
GFP-fusion deletion mutants, fluorescence microscopy, triglyceride quantification in HeLa cells |
PloS one |
Medium |
22194867
|
| 2009 |
The FSP27 CIDE-C domain (aa 174–192) is required for lipid droplet localization and apoptosis induction (via caspase-9 and mitochondrial cytochrome c release); the CIDE-C domain also mediates heterodimerization with CIDEA. |
eGFP-FSP27 deletion constructs, caspase activity assays, cytochrome c release, co-immunoprecipitation, Western blot |
American journal of physiology. Endocrinology and metabolism |
Medium |
19843876
|
| 2014 |
FSP27 (aa 120–220) directly interacts with ATGL (adipose triglyceride lipase) to inhibit its lipolytic activity and promote triglyceride storage; FSP27 depletion increases lipolysis and impairs insulin signaling via reduced AKT phosphorylation. |
Co-immunoprecipitation, domain deletion mapping, siRNA knockdown, lipolysis assays, AKT phosphorylation assays in human adipocytes and ATGL KO mouse fibroblasts |
The Journal of biological chemistry |
High |
24627478
|
| 2017 |
HDAC6 deacetylates CIDEC at K56 (acetylated by PCAF), leading to CIDEC destabilization and reduced lipid droplet fusion; dietary fatty acids promote CIDEC acetylation by dissociating CIDEC from HDAC6 and increasing CIDEC-PCAF association on the ER, requiring conversion of FAs to triacylglycerols. |
Co-immunoprecipitation, acetylation site mutagenesis, adipocyte-specific Hdac6 KO mice, lipid droplet fusion assays, in vivo obese animal models |
The Journal of clinical investigation |
High |
28287402
|
| 2008 |
Fsp27 expression in ob/ob mouse liver is directly transcriptionally activated by PPARγ (functional PPAR response element in the Fsp27 promoter); hepatic Fsp27 promotes triglyceride accumulation and lipid droplet formation. |
Chromatin immunoprecipitation, reporter assay, adenovirus-mediated overexpression and shRNA knockdown in hepatocytes in vitro and in vivo |
Cell metabolism |
High |
18396136
|
| 2008 |
Cidec transcription is directly activated by PPARγ2 via a PPRE at −219/−207 of the Cidec promoter in adipocytes. |
Chromatin immunoprecipitation, luciferase reporter assay, gel shift assay, promoter mutagenesis |
Biochemical and biophysical research communications |
Medium |
18845124
|
| 2015 |
CIDEC/Fsp27 is a direct transcriptional target of PPARα in hepatocytes; adenoviral silencing of hepatic Fsp27 abolishes fasting-induced liver steatosis without altering plasma lipids, and synergizes with PPARα agonists to reduce diet-induced hepatosteatosis. |
ChIP, reporter assay, adenoviral shRNA silencing in vivo, pharmacological PPARα activation |
Hepatology (Baltimore, Md.) |
Medium |
25418138
|
| 2015 |
The liver-enriched transcription factor CREBH activates transcription of a liver-specific Fsp27β isoform (10 extra N-terminal amino acids) from a distinct promoter; Fsp27β localizes to lipid droplet surfaces, suppresses lipolysis, and promotes lipid droplet enlargement and TG accumulation in liver. |
Promoter identification, reporter assay with constitutively active CREBH, adenoviral overexpression, lipid droplet imaging in hepatocytes |
Hepatology (Baltimore, Md.) |
Medium |
25125366
|
| 2012 |
Fsp27/CIDEC is a CREB target gene in the liver; early fasting induction involves the PKA-CREB-CRTC2 signaling pathway (induced by forskolin, blocked by CREB inhibition); pharmacological or genetic inhibition of fatty acid oxidation increases Fsp27 expression during fasting. |
Promoter reporter assay with CREB, forskolin stimulation, Sirt1 KO animals, etomoxir/Hmgcs2 interference in vivo and in HepG2 cells |
Journal of lipid research |
Medium |
23220584
|
| 2021 |
Cidec undergoes phase separation via multivalent homomeric interactions of its N-terminal domain at LD-LD contact sites, forming gel-like condensates that create lipid-permeable fusion plates for LD fusion; phase separation is required for LD fusion activity. |
In vitro phase separation reconstitution, live-cell imaging, fluorescence recovery experiments, deletion mutants, in vivo LDCS analysis |
Developmental cell |
High |
34508658
|
| 2023 |
Cidec-mediated lipid transfer between LDs occurs through closely apposed phospholipid monolayers at LD-LD interfaces, follows exponential kinetics, and is slowed by increasing the distance between monolayers, as visualized by electron cryo-tomography. |
Electron cryo-tomography, quantitative live fluorescence microscopy of lipid transfer kinetics |
Cell reports |
High |
36800289
|
| 2013 |
Crystal structure of the CIDE-N domain of FSP27 at 2.0 Å resolution reveals a biologically important homodimeric interface similar to the CAD/ICAD heterodimeric complex, providing a structural basis for FSP27-mediated LD growth. |
X-ray crystallography at 2.0 Å resolution |
Biochemical and biophysical research communications |
Medium |
24025675
|
| 2018 |
A polybasic RKKR motif in the linker region of CIDEC interacts with acidic phospholipids via electrostatic attraction to inhibit LD fusion; deletion or mutation of the RKKR motif disrupts protein-lipid interaction and results in enhanced LD fusion and supersized LDs. |
Targeted deletion and GFP-fusion constructs, fluorescence microscopy, phospholipid binding assays |
The Journal of biological chemistry |
Medium |
30361435
|
| 2014 |
AMPK activation induces ubiquitination and proteasomal degradation of FSP27, resulting in LD multilocularization; HSC70 is identified as a novel FSP27-binding protein that promotes FSP27 degradation, while CHIP (E3 ubiquitin ligase) is not required. |
AICAR/phenformin treatment, AMPKα1 knockdown, proteasome inhibition, mass spectrometry, co-immunoprecipitation of endogenous proteins, cycloheximide chase, siRNA knockdown of HSC70 and CHIP |
American journal of physiology. Endocrinology and metabolism |
Medium |
25315694
|
| 2015 |
Cidec interacts with AMPKα1 and promotes its degradation via the ubiquitin-proteasome pathway, thereby promoting adipocyte differentiation; the interaction was confirmed by yeast two-hybrid, co-immunoprecipitation, and co-localization. |
Yeast two-hybrid, co-immunoprecipitation, immunofluorescence co-localization, proteasome inhibition assay |
Biochimica et biophysica acta |
Medium |
26367078
|
| 2018 |
Growth hormone downregulates FSP27 expression by activating MEK/ERK signaling, which phosphorylates PPARγ at Ser273 and promotes its nuclear-to-cytosol translocation; FSP27 overexpression inhibits PPARγ Ser273 phosphorylation and promotes nuclear retention, thus suppressing GH-induced lipolysis. |
Selective inhibitors, constitutively active MEK1 mutant, immunofluorescence, subcellular fractionation, reporter assay, human adipose-derived stromal vascular cells, human subjects |
American journal of physiology. Endocrinology and metabolism |
Medium |
30325658
|
| 2016 |
TNF-α downregulates CIDEC transcription through MEK/ERK-dependent phosphorylation and nuclear export of PPARγ in human adipocytes. |
MEK/ERK inhibitors, constitutively active MEK1, immunofluorescence, subcellular fractionation, luciferase reporter assay |
Obesity (Silver Spring, Md.) |
Medium |
27062372
|
| 2014 |
CIDEC translocates from the ER to lipid droplets in response to fatty acid stimulation; the N-terminal domain (aa 1–173) mediates LD localization while the C-terminal domain (aa 174–238) is necessary for LD fusion; aa 106–173 contains an ER-binding domain. |
CIDEC deletion mutant analysis, immunofluorescence, subcellular fractionation in HepG2 cells |
Genes to cells : devoted to molecular & cellular mechanisms |
Medium |
25255829
|
| 2022 |
CIDEC regulates ATGL enzymatic activity by interacting with its activator CGI-58, reducing free fatty acid release and lipotoxicity in adipocytes; adipose-specific CIDEC transgenic mice are protected from HFD-induced glucose intolerance, while the E186X variant abolishes this protection. |
Transgenic mouse model (Ad-CIDECtg and Ad-CIDECmut), transcriptomics, lipidomics, Co-IP of CIDEC-CGI-58, recombinant CIDEC treatment of human adipose tissue, triglyceride breakdown assays |
The Journal of biological chemistry |
High |
35963433
|
| 2023 |
CIDEC interacts with endothelial VEGFA-VEGFR2 signaling; endothelial-specific CIDEC expression reduces VEGFA and VEGFR2 degradation, increasing VEGFR2 activation, improved insulin signaling/eNOS activation, and vascular relaxation. |
Endothelial-specific CIDEC transgenic mice, insulin signaling assays, eNOS activation, vascular relaxation measurements, VEGF pathway analysis |
Diabetes |
Medium |
36256836
|
| 2022 |
Small intestine-specific CIDEC knockout reduces body fat, liver TG, and hepatic steatosis; mechanistically, CIDEC promotes phosphatidic acid synthesis by interacting with 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT) to accelerate TG accumulation in intestinal cells. |
Cre/LoxP intestine-specific KO mice, Co-IP of CIDEC-AGPAT, metabolic phenotyping, phosphatidic acid measurement |
International journal of biological sciences |
Medium |
36263170
|
| 2023 |
Paxillin family proteins Hic-5 and LPXN interact with CIDEC and inhibit its proteasomal ubiquitination/degradation, thereby stabilizing CIDEC protein, enlarging LDs, and promoting lipid storage in adipocytes. |
HTRF-based high-throughput screening, Co-IP, ubiquitination assays, proteasome inhibition, LD morphology in adipocytes |
The Journal of biological chemistry |
Medium |
38159847
|
| 2010 |
Insulin upregulates CIDEC expression in human adipocytes via a PI3K-JNK2-dependent pathway, and CIDEC depletion abolishes insulin-induced lipid droplet enlargement and increases glycerol release. |
PI3K/Akt/JNK inhibitors, siRNA knockdown of JNK1/JNK2, lipid droplet imaging, glycerol release assay |
Journal of lipid research |
Medium |
20154362 21636835
|
| 2016 |
FSP27 negatively regulates AMPK activity and ATGL expression in adipocytes; CIDEC knockdown in LPS-treated renal tubular epithelial cells restores phospho-AMPKα and suppresses NF-κB pathway activation and inflammatory cytokine production. |
CIDEC siRNA knockdown, Western blot for p-AMPKα, NF-κB pathway reporters, cytokine measurement |
Inflammation |
Low |
29959627
|
| 2017 |
Gp78 (membrane E3 ubiquitin ligase) co-localizes and physically interacts with CIDEC on the surface of lipid droplets, and this interaction promotes lipid accumulation in hepatocytes. |
Co-immunoprecipitation, immunofluorescence co-localization, overexpression/knockdown in AML12 cells |
Molecular medicine reports |
Low |
28656280
|
| 2016 |
FSP27 negatively regulates the AMPK-signaling axis; negatively charged residues (D215, E218, E219, E220) in the polar C-terminal region of FSP27 are essential for LD enlargement, while the N-terminal domain (aa 1–130) accelerates but is not required for LD growth. |
FSP27 domain deletion and charge-reversal mutagenesis, LD size quantification |
FEBS letters |
Medium |
26921608
|
| 2003 |
Human CIDE-3 (CIDEC), a homologue of mouse FSP27, contains conserved CIDE-N and CIDE-C domains and induces apoptosis (DNA fragmentation) upon overexpression in 293T cells; GFP-tagged CIDE-3 localizes to cytosolic corpuscles; an alternative splice isoform (CIDE-3α, lacking exon 3) retains apoptosis-inducing activity. |
DNA fragmentation assay, GFP fusion protein localization, RT-PCR, transfection in 293T cells |
The Biochemical journal |
Medium |
12429024
|
| 2010 |
CIDE-3 (CIDEC) interacts with LITAF (lipopolysaccharide-induced tumor necrosis factor) in hepatic cells, identified by yeast two-hybrid screening; overexpressed CIDE-3 induces apoptosis in hepatocellular carcinoma cells. |
Yeast two-hybrid, flow cytometry apoptosis assay, overexpression in SMMC-7721 cells |
Medical oncology (Northwood, London, England) |
Low |
20957525
|
| 1992 |
The FSP27 promoter confers adipocyte-specific expression; a palindromic sequence (TTCGAAA) is required for adipocyte-specific expression and is bound by C/EBP and C/EBP-like proteins as demonstrated by DNase I footprinting. |
Promoter-reporter transfection, DNase I footprinting with nuclear extracts |
The Journal of biological chemistry |
Medium |
1339452
|
| 2025 |
CIDEC acts as a metabolic gatekeeper in liver regeneration: its depletion after peak LD accumulation promotes TG mobilization and fatty acid oxidation-driven regeneration; overexpression of CIDEC or DGAT2 exacerbates TG retention and impairs regeneration. |
CIDEC depletion/overexpression in mice, lipidomics, transcriptomics, FAO inhibition experiments, chronic steatosis model |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
41255220
|
| 2025 |
N-terminal domain of CIDEC (CIDEC-N) undergoes phase separation in vitro; in vitro reconstitution confirmed that multivalent homomeric CIDEC-N interactions are sufficient to drive phase separation, providing a biochemical basis for LDCS condensate formation. |
Recombinant protein purification, in vitro phase separation assay, concentration-dependent droplet formation |
STAR protocols |
Medium |
40232936
|