Affinage

CIDEC

Lipid transferase CIDEC · UniProt Q96AQ7

Length
238 aa
Mass
26.8 kDa
Annotated
2026-06-09
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CIDEC (FSP27) is a lipid droplet (LD)-associated protein that drives the formation of unilocular, enlarged LDs and promotes triglyceride storage in adipocytes and hepatocytes; its loss in mice produces multilocular LDs, elevated lipolysis, reduced TG storage, and a 'browning' of white adipose tissue with increased mitochondrial activity (PMID:18654663, PMID:18682832). Mechanistically, CIDEC enriches at LD–LD contact sites and mediates directional, pressure-driven net lipid transfer from smaller to larger LDs, leading to clustering and fusion (PMID:22144693, PMID:22194867). This activity depends on homodimerization of its CIDE-N domain—whose crystal structure reveals a CAD/ICAD-like dimeric interface—and on phase separation of its multivalent N-terminus, which forms gel-like condensates that create lipid-permeable 'fusion plates' between closely apposed LD monolayers (PMID:23481402, PMID:24025675, PMID:34508658, PMID:36800289). The fusogenic activity is amplified by interaction with perilipin1 (PLIN1) through the CIDE-N domain and is autoinhibited by a polybasic RKKR linker motif that binds acidic phospholipids (PMID:23481402, PMID:30361435). CIDEC suppresses lipolysis by binding the lipase ATGL and its activator CGI-58, thereby limiting free fatty acid release, protecting against lipotoxicity and free-fatty-acid-induced insulin resistance, and maintaining insulin sensitivity (PMID:24627478, PMID:35963433). CIDEC expression is transcriptionally controlled in a tissue-specific manner by PPARγ during adipogenesis and in liver, by CREBH (Fsp27β) and PPARα in hepatocytes, and is down-regulated by TNF-α/growth hormone via MEK/ERK-driven PPARγ Ser273 phosphorylation (PMID:18845124, PMID:18396136, PMID:25125366, PMID:25418138, PMID:27062372, PMID:30325658). CIDEC protein stability is set by post-translational mechanisms: AMPK activation triggers ubiquitin-proteasome degradation (with HSC70 as a stabilizing chaperone), HDAC6-mediated deacetylation at K56 destabilizes it while PCAF acetylation stabilizes it, and paxillin-family proteins Hic-5/LPXN reduce its ubiquitination (PMID:25315694, PMID:28287402, PMID:38159847). A homozygous nonsense CIDEC mutation (E186X) disrupting the CIDE-C domain causes protein mislocalization, failure of LD enlargement, and partial lipodystrophy with multiloculated adipocyte LDs in humans (PMID:20049731).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1992 High

    Before any functional role was known, the question was what restricts FSP27 expression to fat cells; identifying the adipocyte-specific promoter element established it as a differentiation-linked gene.

    Evidence Reporter transfection, DNase I footprinting, and gel shift with adipocyte nuclear extracts identifying a C/EBP-bound palindromic element

    PMID:1339452

    Open questions at the time
    • Did not connect promoter activity to a protein function
    • C/EBP regulation not linked to later PPARγ axis
  2. 2003 Medium

    An early functional annotation tested whether the human ortholog (CIDE-3) acted in cell death, framing CIDEC initially as a pro-apoptotic factor rather than a lipid regulator.

    Evidence DNA fragmentation assay and GFP localization after ectopic expression in 293T cells, including a splice isoform

    PMID:12429024

    Open questions at the time
    • Apoptosis seen only on overexpression in non-adipose cells
    • No endogenous role demonstrated
    • Relationship to lipid storage not addressed
  3. 2008 High

    The defining question—what does CIDEC do physiologically—was answered by showing it is required for unilocular LD formation and TG storage, with knockout causing multilocular droplets and increased lipolysis.

    Evidence FSP27 knockout mice, adipocyte siRNA, ectopic expression in COS cells with LD morphology and lipolysis assays

    PMID:18654663

    Open questions at the time
    • Molecular mechanism of LD enlargement unknown
    • Direct binding partners not yet identified
  4. 2008 High

    Parallel work established CIDEC's transcriptional control and tissue reach, showing it is a direct PPARγ target driving hepatic TG accumulation and a regulator of WAT identity whose loss browns adipose tissue.

    Evidence PPRE identification, ChIP/reporter assays, adenoviral gain/loss-of-function in hepatocytes, and KO mouse mitochondrial/gene-expression analyses

    PMID:18396136 PMID:18682832 PMID:18845124

    Open questions at the time
    • How TG storage feeds back on mitochondrial/browning genes unresolved
    • Tissue-specific promoter usage not yet distinguished
  5. 2009 High

    Domain dissection and human genetics localized function to the CIDE-C domain, establishing it as essential for LD targeting and enlargement and causally linking CIDEC loss to human lipodystrophy.

    Evidence Deletion constructs/LD localization in HeLa, co-IP with CIDEA, and an E186X nonsense mutation in a partial lipodystrophy patient

    PMID:19843876 PMID:20049731

    Open questions at the time
    • Mechanism by which CIDE-C anchors to LD not defined
    • Apoptosis vs. lipid functions of the domain not separated
  6. 2011 High

    The central mechanistic advance defined CIDEC as a lipid-transfer/fusion machine: it enriches at LD–LD contact sites and mediates directional, pressure-driven net lipid transfer from small to large LDs, with domains mapped for clustering versus fusion.

    Evidence FRAP and live-cell imaging in KO vs. expressing adipocytes, plus systematic GFP-deletion domain mapping

    PMID:22144693 PMID:22194867

    Open questions at the time
    • Structural basis of the transfer conduit not yet resolved
    • How directionality is set beyond pressure inference unclear
  7. 2013 High

    The molecular requirements for lipid transfer were defined: CIDE-N homodimerization (with a crystal structure) drives transfer, and PLIN1 binding to CIDE-N markedly potentiates it.

    Evidence Reciprocal co-IP, FRAP, mutagenesis of the dimer interface, rescue by PLIN1, and a 2.0 Å CIDE-N crystal structure

    PMID:23399566 PMID:23481402 PMID:24025675

    Open questions at the time
    • How dimerization couples to monolayer permeabilization unknown
    • Stoichiometry at contact sites not defined
  8. 2014 High

    CIDEC's anti-lipolytic mechanism was identified—direct interaction with ATGL inhibits lipolysis and protects against free-fatty-acid-induced insulin resistance—connecting LD storage to metabolic health.

    Evidence Co-IP, FSP27/ATGL siRNA, ATGL-KO fibroblasts, lipolysis assays, and phospho-AKT readouts

    PMID:24627478

    Open questions at the time
    • Whether inhibition is steric or allosteric unclear
    • CGI-58 involvement not yet addressed
  9. 2014 High

    Protein stability was shown to be actively regulated: AMPK activation drives ubiquitin-proteasome degradation of CIDEC while HSC70 stabilizes it, providing a route to dynamically control LD architecture.

    Evidence Co-IP/MS, cycloheximide chase, siRNA, and ubiquitination assays under AICAR/phenformin

    PMID:25315694

    Open questions at the time
    • E3 ligase not identified
    • Link between degradation and metabolic state incomplete
  10. 2015 High

    Tissue-specific transcriptional logic was extended in liver, where CREBH drives the Fsp27β promoter and PPARα drives fasting-induced hepatic CIDEC, defining context-dependent isoform control of steatosis.

    Evidence Promoter reporter assays, CREBH-KO and PPARα ChIP/reporter, in vivo adenoviral/ASO silencing in fasting models

    PMID:25125366 PMID:25418138

    Open questions at the time
    • How α vs. β isoforms differ functionally beyond promoter usage unclear
    • Cross-talk between hepatic and adipose programs unaddressed
  11. 2017 High

    Acetylation was added as a stability switch: PCAF acetylation at K56 stabilizes CIDEC and promotes LD fusion, while HDAC6 deacetylation destabilizes it, with fatty acids biasing toward acetylation.

    Evidence Adipocyte Hdac6-KO mice, co-IP/MS, K56 mutagenesis, and LD fusion assays

    PMID:28287402

    Open questions at the time
    • How K56 acetylation alters fusion mechanistically unclear
    • Interplay with AMPK/ubiquitin pathway not integrated
  12. 2018 High

    The fusion machinery was shown to be autoinhibited: a polybasic RKKR linker binds acidic phospholipids to limit fusion, defining a built-in brake on supersized LD formation.

    Evidence Deletion/charge mutation of the RKKR linker with LD-size quantification

    PMID:30361435

    Open questions at the time
    • How phospholipid binding is relieved physiologically unclear
    • Relationship to PLIN1 activation not resolved
  13. 2021 High

    The physical mechanism of fusion-plate formation was revealed: CIDEC undergoes phase separation via its multivalent N-terminus to form gel-like condensates that create lipid-permeable passageways between LDs.

    Evidence In vitro phase-separation reconstitution, super-resolution and live imaging, FRAP, and deletion constructs

    PMID:34508658

    Open questions at the time
    • Composition of the permeable sub-compartments incompletely defined
    • Regulation of condensate state by PTMs unaddressed
  14. 2023 High

    High-resolution structural and kinetic analysis confirmed pressure-driven lipid transfer through closely apposed, 'leaky' monolayers, with transfer rate set by inter-monolayer distance.

    Evidence Electron cryo-tomography of LD–LD interfaces with quantitative live transfer kinetics

    PMID:36800289

    Open questions at the time
    • Atomic structure of the pore/passage not resolved
    • How CIDEC sculpts monolayer apposition unclear
  15. 2023 Medium

    Stability regulation was broadened by identifying paxillin-family proteins Hic-5 and LPXN as binders that reduce CIDEC ubiquitination, promoting LD enlargement.

    Evidence HTRF screen, co-IP, siRNA, proteasome inhibition, and LD imaging

    PMID:38159847

    Open questions at the time
    • Single-lab interaction without reciprocal in vivo validation
    • Mechanism of ubiquitination protection unclear
  16. 2022 High

    The anti-lipolytic mechanism was refined and tied to metabolic protection: CIDEC engages ATGL's activator CGI-58 to limit free fatty acid release, and transgenic CIDEC (not E186X) protects against diet-induced glucose intolerance.

    Evidence Adipose-specific CIDEC transgenic mice, co-IP, lipidomics, and recombinant CIDEC on human adipose tissue

    PMID:35963433

    Open questions at the time
    • Whether CGI-58 sequestration is the sole anti-lipolytic route unclear
    • Quantitative contribution vs. direct ATGL binding not separated
  17. 2025 High

    Beyond storage, CIDEC was placed in dynamic lipid mobilization: its depletion after peak LD accumulation promotes TG mobilization via fatty acid oxidation to support liver regeneration.

    Evidence CIDEC KO/overexpression mice, DGAT2 overexpression, etomoxir FAO inhibition, lipidomics in a partial hepatectomy model

    PMID:41255220

    Open questions at the time
    • How CIDEC down-regulation is timed during regeneration unclear
    • Direct link between LD architecture and FAO substrate availability not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple stability/PTM inputs (AMPK-ubiquitin, K56 acetylation, paxillin binding), the RKKR autoinhibition, and PLIN1 activation are integrated to set CIDEC condensate state and fusion output at a given metabolic state remains unresolved.
  • No unified model coupling PTM state to phase-separation/fusion activity
  • E3 ligase for AMPK-driven degradation unidentified
  • Atomic structure of the lipid-transfer conduit lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0140104 molecular carrier activity 2
Localization
GO:0005811 lipid droplet 5 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-392499 Metabolism of proteins 3

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
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

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets. The Journal of clinical investigation 333 18654663
2011 Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites. The Journal of cell biology 304 22144693
2008 Hepatic steatosis in leptin-deficient mice is promoted by the PPARgamma target gene Fsp27. Cell metabolism 297 18396136
2008 Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice. PloS one 223 18682832
2013 Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes. Nature communications 215 23481402
2009 Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. EMBO molecular medicine 212 20049731
2015 Fat-Specific Protein 27/CIDEC Promotes Development of Alcoholic Steatohepatitis in Mice and Humans. Gastroenterology 124 26099526
2013 FSP27 and PLIN1 interaction promotes the formation of large lipid droplets in human adipocytes. Biochemical and biophysical research communications 113 23399566
2011 FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation. PloS one 108 22194867
2003 Molecular cloning and characterization of CIDE-3, a novel member of the cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector family. The Biochemical journal 103 12429024
2014 Fat-specific protein 27 (FSP27) interacts with adipose triglyceride lipase (ATGL) to regulate lipolysis and insulin sensitivity in human adipocytes. The Journal of biological chemistry 100 24627478
1992 Cloning and transcriptional regulation of a novel adipocyte-specific gene, FSP27. CAAT-enhancer-binding protein (C/EBP) and C/EBP-like proteins interact with sequences required for differentiation-dependent expression. The Journal of biological chemistry 98 1339452
2015 Transcriptional activation of Fsp27 by the liver-enriched transcription factor CREBH promotes lipid droplet growth and hepatic steatosis. Hepatology (Baltimore, Md.) 90 25125366
2015 Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice. Nature communications 87 25565658
2018 FTO promotes SREBP1c maturation and enhances CIDEC transcription during lipid accumulation in HepG2 cells. Biochimica et biophysica acta. Molecular and cell biology of lipids 73 29486327
2009 Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA. American journal of physiology. Endocrinology and metabolism 73 19843876
2015 CIDEC/FSP27 is regulated by peroxisome proliferator-activated receptor alpha and plays a critical role in fasting- and diet-induced hepatosteatosis. Hepatology (Baltimore, Md.) 70 25418138
2017 HDAC6-mediated acetylation of lipid droplet-binding protein CIDEC regulates fat-induced lipid storage. The Journal of clinical investigation 69 28287402
2008 Assessment of fat-specific protein 27 in the adipocyte lineage suggests a dual role for FSP27 in adipocyte metabolism and cell death. American journal of physiology. Endocrinology and metabolism 60 18198355
2008 Transcriptional activation of Cidec by PPARgamma2 in adipocyte. Biochemical and biophysical research communications 60 18845124
2008 Lipid droplets: FSP27 knockout enhances their sizzle. The Journal of clinical investigation 52 18654644
2018 Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes. American journal of physiology. Endocrinology and metabolism 48 30325658
2011 Loss of mitogen-activated protein kinase phosphatase-1 protects from hepatic steatosis by repression of cell death-inducing DNA fragmentation factor A (DFFA)-like effector C (CIDEC)/fat-specific protein 27. The Journal of biological chemistry 48 21521693
2021 A gel-like condensation of Cidec generates lipid-permeable plates for lipid droplet fusion. Developmental cell 44 34508658
2012 Comparison of brown and white adipose tissue fat fractions in ob, seipin, and Fsp27 gene knockout mice by chemical shift-selective imaging and (1)H-MR spectroscopy. American journal of physiology. Endocrinology and metabolism 41 23149622
2010 Human adenovirus 36 decreases fatty acid oxidation and increases de novo lipogenesis in primary cultured human skeletal muscle cells by promoting Cidec/FSP27 expression. International journal of obesity (2005) 41 20440297
2016 Polychlorinated biphenyls exposure-induced insulin resistance is mediated by lipid droplet enlargement through Fsp27. Archives of toxicology 35 27837308
2012 Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate. Journal of lipid research 34 23220584
2016 TNF-α downregulates CIDEC via MEK/ERK pathway in human adipocytes. Obesity (Silver Spring, Md.) 33 27062372
2010 Differential roles of CIDEA and CIDEC in insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes. Journal of lipid research 32 20154362
2018 Growth hormone controls lipolysis by regulation of FSP27 expression. The Journal of endocrinology 31 30400015
2017 Amelioration of diet-induced steatohepatitis in mice following combined therapy with ASO-Fsp27 and fenofibrate. Journal of lipid research 28 28874443
2011 Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes. Journal of lipid research 28 21636835
2015 Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice. PloS one 27 26176546
2022 Ban-xia-xie-xin-tang ameliorates hepatic steatosis by regulating Cidea and Cidec expression in HFD-fed mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 25 35908522
2019 Pgc1a is responsible for the sex differences in hepatic Cidec/Fsp27β mRNA expression in hepatic steatosis of mice fed a Western diet. American journal of physiology. Endocrinology and metabolism 25 31846369
2018 Dietary fat-associated osteoarthritic chondrocytes gain resistance to lipotoxicity through PKCK2/STAMP2/FSP27. Bone research 25 30002945
2018 Effects of a high energy and low protein diet on hepatic and plasma characteristics and Cidea and Cidec mRNA expression in liver and adipose tissue of laying hens with fatty liver hemorrhagic syndrome. Animal science journal = Nihon chikusan Gakkaiho 25 30523654
2023 The architecture of Cidec-mediated interfaces between lipid droplets. Cell reports 21 36800289
2022 Human CIDEC transgene improves lipid metabolism and protects against high-fat diet-induced glucose intolerance in mice. The Journal of biological chemistry 21 35963433
2022 Small Intestine-specific Knockout of CIDEC Improves Obesity and Hepatic Steatosis by Inhibiting Synthesis of Phosphatidic Acid. International journal of biological sciences 19 36263170
2010 Cide-a and Cide-c are induced in the progression of hepatic steatosis and inhibited by eicosapentaenoic acid. Prostaglandins, leukotrienes, and essential fatty acids 19 20542418
2019 Mouse Fat-Specific Protein 27 (FSP27) expressed in plant cells localizes to lipid droplets and promotes lipid droplet accumulation and fusion. Biochimie 18 31400447
2015 Cidec promotes the differentiation of human adipocytes by degradation of AMPKα through ubiquitin-proteasome pathway. Biochimica et biophysica acta 18 26367078
2014 Effects of pioglitazone mediated activation of PPAR-γ on CIDEC and obesity related changes in mice. PloS one 17 25210844
2014 Regulation of FSP27 protein stability by AMPK and HSC70. American journal of physiology. Endocrinology and metabolism 17 25315694
2013 Molecular basis for homo-dimerization of the CIDE domain revealed by the crystal structure of the CIDE-N domain of FSP27. Biochemical and biophysical research communications 17 24025675
2010 CIDE-3 interacts with lipopolysaccharide-induced tumor necrosis factor, and overexpression increases apoptosis in hepatocellular carcinoma. Medical oncology (Northwood, London, England) 17 20957525
2018 Polybasic RKKR motif in the linker region of lipid droplet (LD)-associated protein CIDEC inhibits LD fusion activity by interacting with acidic phospholipids. The Journal of biological chemistry 16 30361435
2020 Eicosapentaenoic and docosapentaenoic acids lessen the expression of PPARγ/Cidec affecting adipogenesis in cultured 3T3-L1 adipocytes. Acta histochemica 15 31955908
2017 The effects of cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) on milk lipid synthesis in mammary glands of dairy cows. Journal of dairy science 15 28284693
2008 Molecular cloning, chromosomal location and expression pattern of porcine CIDEa and CIDEc. Molecular biology reports 15 18311595
2021 CIDEC silencing attenuates diabetic nephropathy via inhibiting apoptosis and promoting autophagy. Journal of diabetes investigation 14 33655702
2024 Exosomes as nanostructures deliver miR-204 in alleviation of mitochondrial dysfunction in diabetic nephropathy through suppressing methyltransferase-like 7A-mediated CIDEC N6-methyladenosine methylation. Aging 13 38334961
2019 Plasticity of histone modifications around Cidea and Cidec genes with secondary bile in the amelioration of developmentally-programmed hepatic steatosis. Scientific reports 13 31745102
2018 CIDEC Is Involved in LPS-Induced Inflammation and Apoptosis in Renal Tubular Epithelial Cells. Inflammation 13 29959627
2017 Cidec differentially regulates lipid deposition and secretion through two tissue-specific isoforms. Gene 13 29080839
2022 Metformin Inhibits Lipid Droplets Fusion and Growth via Reduction in Cidec and Its Regulatory Factors in Rat Adipose-Derived Stem Cells. International journal of molecular sciences 12 35682666
2022 AMPK-PPARγ-Cidec Axis Drives the Fasting-Induced Lipid Droplet Aggregation in the Liver of Obese Mice. Frontiers in nutrition 11 35859752
2019 FSP27 and Links to Obesity and Diabetes Mellitus. Current obesity reports 11 30919313
2014 Translocation of CIDEC in hepatocytes depends on fatty acids. Genes to cells : devoted to molecular & cellular mechanisms 11 25255829
2023 Endothelial-Specific Expression of CIDEC Improves High-Fat Diet-Induced Vascular and Metabolic Dysfunction. Diabetes 10 36256836
2021 Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) regulates acetate- and β-hydroxybutyrate-induced milk fat synthesis by increasing FASN expression in mammary epithelial cells of dairy cows. Journal of dairy science 10 33663853
2021 Cell death-inducing DFFA-like effector C/CIDEC gene silencing alleviates diabetic cardiomyopathy via upregulating AMPKa phosphorylation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 33913563
2020 Eicosapentaenoic acid-enriched phospholipids suppressed lipid accumulation by specific inhibition of lipid droplet-associated protein FSP27 in mice. Journal of the science of food and agriculture 10 31919850
2021 Inhibition of cell death inducing DNA fragmentation factor-α-like effector c (CIDEC) by tumor necrosis factor-α induces lipolysis and inflammation in calf adipocytes. Journal of dairy science 9 33685683
2016 Regulation of PPARγ and CIDEC expression by adenovirus 36 in adipocyte differentiation. Molecular and cellular biochemistry 9 27995415
2018 Therapeutic silencing of FSP27 reduces the progression of atherosclerosis in Ldlr-/- mice. Atherosclerosis 8 29859472
2017 Role of glycoprotein 78 and cidec in hepatic steatosis. Molecular medicine reports 8 28656280
2024 CIDEC/FSP27 exacerbates obesity-related abdominal aortic aneurysm by promoting perivascular adipose tissue inflammation. Life metabolism 7 39872985
2019 Involvement of PPARγ/FSP27 in the pathogenic mechanism underlying insulin resistance: tipping the balance between lipogenesis and fat storage in adult catch-up growth rats. Nutrition & metabolism 7 30792748
2016 Negatively-charged residues in the polar carboxy-terminal region in FSP27 are indispensable for expanding lipid droplets. FEBS letters 7 26921608
2015 Haplotypes in the promoter region of the CIDEC gene associated with growth traits in Nanyang cattle. Scientific reports 7 26189824
2024 Attenuation of brown adipocyte whitening in high-fat diet-induced obese rats: Effects of melatonin and β-hydroxybutyrate on Cidea, Fsp27 and MT1 expression. Diabetes, obesity & metabolism 6 39118207
2017 Single nucleotide polymorphisms in CIDEC gene are associated with metabolic syndrome components risks and antihypertensive drug efficacy. Oncotarget 6 28415694
2016 Alcohol and fat promote steatohepatitis: a critical role for fat-specific protein 27/CIDEC. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 6 27342423
2023 Rare CIDEC coding variants enriched in age-related macular degeneration patients with small low-luminance deficit cause lipid droplet and fat storage defects. PloS one 5 37079518
2022 Fsp27 plays a crucial role in muscle performance. American journal of physiology. Endocrinology and metabolism 5 35157807
2013 Cell death-inducing DFFA-like effector c (CIDEC/Fsp27) gene: molecular cloning, sequence characterization, tissue distribution and polymorphisms in Chinese cattles. Molecular biology reports 5 24065549
2023 Paxillin family proteins Hic-5 and LPXN promote lipid storage by regulating the ubiquitination degradation of CIDEC. The Journal of biological chemistry 4 38159847
2012 [Novel mechanism for hepatic lipid accumulation: a physiological role for hepatic PPARγ-fsp27 signal]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 4 22790028
2019 Bariatric Surgery in Rats Upregulates FSP27 Expression in Fat Tissue to Affect Fat Hydrolysis and Metabolism. BioMed research international 3 31205943
2017 Distribution and quantitative analysis of CIDEa and CIDEc in broiler chickens: accounting for differential fat deposition between strains. British poultry science 3 29219006
2016 The role of expression imbalance between adipose synthesis and storage mediated by PPAR-γ/FSP27 in the formation of insulin resistance in catch up growth. Lipids in health and disease 3 27716232
2015 Polymorphisms in the bovine CIDEC gene are associated with body measurement traits and meat quality traits in Qinchuan cattle. Genetics and molecular research : GMR 3 26345833
2012 Purification, crystallization and preliminary X-ray crystallographic analysis of the CIDE-N domain of Fsp27. Acta crystallographica. Section F, Structural biology and crystallization communications 3 23192040
2025 Comparative effect of high intensity interval training and moderate intensity continuous training on metabolic improvements and regulation of Cidea and Cidec in obese C57BL/6 mice. PloS one 2 40305497
2025 Partial inhibition of adipose CIDEC improves insulin sensitivity and increases energy expenditure in high-fat diet-fed mice via activating ATGL-PPARα pathway. Biochimica et biophysica acta. Molecular and cell biology of lipids 2 40633832
2025 CIDEC Restricts Liver Regeneration by Disturbing Lipid Droplet Triglyceride Turnover. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 41255220
2022 CIDEC: A Potential Factor in Diabetic Vascular Inflammation. Journal of vascular research 2 35124674
2019 CIDEA and CIDEC are regulated by CREB and are not induced during fasting in grass carp Ctenopharyngodon idella adipocytes. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 2 31028911
2006 [Construction of the prokaryotic expression vector and expression of human CIDE-3 gene]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 2 16507259
2026 Novel Homozygous Variants in CIDEC and WRN in a Young Female with Lipodystrophy and Thyroid Cancer. International journal of molecular sciences 1 41596298
2025 Protocol for in vitro phase separation of N terminus of CIDEC proteins. STAR protocols 1 40232936
2025 ApoA5-CIDEC axis regulates hepatic lipid metabolism, inflammation, and fibrosis in MASLD. Journal of molecular medicine (Berlin, Germany) 1 41392209
2019 A Novel Proangiogenic Function of Fsp27 in Endothelium: You Only Live Thrice? Journal of the American Heart Association 1 31433705
2013 Crystallization and preliminary X-ray crystallographic studies of the CIDE-N domain of CIDE-3. Acta crystallographica. Section F, Structural biology and crystallization communications 1 24192364
2025 CIDEC is most closely associated with fat storage in human adipose tissue among CIDE family isoforms in severely obese subjects: a cross-sectional study. Diabetology international 0 40607154
2025 Whole-body Loss of FSP27 Impairs Cognitive Function via Disruption of Neuro-Metabolic Pathways. bioRxiv : the preprint server for biology 0 40766532
2013 [Research advances on CIDEC in insulin resistance]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 0 24229606

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