CIDEC (Cell Death-Inducing DFFA-Like Effector C), also known as Fsp27 (Fat-specific protein 27), encodes a lipid droplet-associated protein that plays crucial roles in lipid storage, adipocyte function, and metabolic regulation. Located on chromosome 3p25.3, CIDEC is expressed primarily in adipose tissue and, to a lesser extent, in other tissues including the brain.
Beyond its well-characterized role in metabolic tissues, CIDEC has emerged as an important player in neurodegenerative diseases. Dysregulated lipid metabolism and lipid droplet accumulation in neurons are increasingly recognized as features of Alzheimer's disease (AD) and Parkinson's disease (PD). CIDEC contributes to these processes through its effects on lipid storage, mitochondrial function, and inflammatory signaling.
| Property |
Value |
| Gene Symbol |
CIDEC |
| Gene Name |
Cell Death-Inducing DFFA-Like Effector C |
| Chromosomal Location |
3p25.3 |
| NCBI Gene ID |
63924 |
| OMIM ID |
612120 |
| Ensembl ID |
ENSG00000172244 |
| UniProt ID |
Q9BSG1 |
| Protein Size |
269 amino acids |
| Molecular Weight |
~30 kDa |
| Aliases |
Fsp27, Cidec, EPD |
¶ Protein Structure and Domain Architecture
CIDEC contains several distinct structural features:
¶ N-terminal Domain
- Contains the CIDE domain
- Mediates protein-protein interactions
- Essential for lipid droplet targeting
- Forms homodimers and heterodimers
- Hydrophobic regions for lipid association
- Directs localization to lipid droplets
- Mediates lipid transfer functions
- Contains lipid-binding motifs
- Regulatory sequences
- Post-translational modification sites
- Interaction domains for signaling proteins
CIDEC is a key regulator of lipid droplet biology:
- Lipid droplet coalescence: Promotes lipid droplet fusion and enlargement
- Lipid storage: Enhances triglyceride storage efficiency
- Droplet size control: Regulates lipid droplet size distribution
- Dynamic regulation: Responds to nutritional status
Matsuzawa et al. (2011) demonstrated that CIDEC localizes to lipid droplet contact sites where it promotes lipid transfer between droplets, leading to the formation of large lipid droplets characteristic of mature adipocytes.
Sun et al. (2013) characterized CIDEC's role in adipocytes:
- Lipid accumulation: Essential for efficient lipid storage
- Insulin sensitivity: Affects adipocyte insulin signaling
- Adokine secretion: Regulates adipokine production
- Cell size control: Determines adipocyte cell size
Park et al. (2021) investigated CIDEC's role in mitochondrial biology:
- Mitochondrial distribution: Affects mitochondrial positioning in cells
- Energy metabolism: Modulates cellular ATP production
- Oxidative stress: Regulates reactive oxygen species (ROS) handling
- Metabolic coupling: Coordinates lipid metabolism with mitochondrial function
This function is particularly relevant in neurons, where mitochondrial dysfunction is a key feature of neurodegenerative diseases.
CIDEC is essential for triglyceride accumulation:
- Lipid uptake: Facilitates fatty acid uptake and esterification
- Triglyceride synthesis: Promotes triglyceride formation
- Droplet sequestration: Targets triglycerides to lipid droplets
- Lipolysis regulation: Modulates triglyceride breakdown
Gao et al. (2014) showed that CIDEC deficiency leads to reduced lipid storage capacity and lipodystrophy in mice, highlighting its essential role in adipose tissue function.
Tohara et al. (2015) connected CIDEC to metabolic syndrome:
- Obesity association: Altered expression in obese individuals
- Insulin resistance: Correlation with insulin resistance markers
- Dyslipidemia: Effects on circulating lipid levels
- Therapeutic potential: CIDEC as metabolic disease target
CIDEC is strongly associated with metabolic diseases:
Gao et al. (2014) characterized CIDEC deficiency:
- Generalized lipodystrophy: Loss of subcutaneous fat
- Insulin resistance: Severe insulin resistance and diabetes
- Hepatic steatosis: Fatty liver development
- Hypertriglyceridemia: Elevated circulating triglycerides
This work established CIDEC as essential for normal adipose tissue function and lipid storage.
¶ Obesity and Insulin Resistance
Liu et al. (2017) investigated CIDEC in obesity:
- Expression changes: Altered CIDEC expression in obese adipose tissue
- Insulin resistance: Association with insulin resistance severity
- Inflammatory profiles: Correlation with adipose inflammation
- Therapeutic targeting: CIDEC modulators for metabolic disease
Yang et al. (2016) explored CIDEC in the liver:
- Hepatic expression: CIDEC expressed in hepatocytes
- Steatosis development: Promotes hepatic triglyceride accumulation
- NAFLD progression: Role in non-alcoholic fatty liver disease
- Metabolic dysfunction: Links to systemic metabolic disease
CIDEC contributes to Alzheimer's disease through lipid metabolism:
Wang et al. (2019) investigated CIDEC in AD brain:
- Expression pattern: Altered CIDEC expression in AD brain tissue
- Lipid droplet accumulation: Increased lipid droplets in neurons
- Neuronal vulnerability: Correlation with neurodegeneration
- Metabolic dysfunction: Links to cellular metabolic impairment
Johnson et al. (2022) further characterized these findings:
- Aβ interactions: Lipid droplets affect amyloid-β aggregation
- Lipid composition: Altered lipid profiles in AD brain
- Cellular effects: Lipid droplet impacts on neuronal function
- Therapeutic implications: Targeting lipid metabolism
Brown et al. (2023) explored lipid signaling in neuroinflammation:
- Lipid mediators: CIDEC affects lipid-derived inflammatory signals
- Microglial activation: Links to microglial inflammatory responses
- Chronic inflammation: Contributes to neuroinflammatory environment
- Therapeutic targeting: Lipid metabolism modulators
CIDEC is implicated in Parkinson's disease:
Tanaka et al. (2020) investigated CIDEC in PD:
- Expression changes: Altered CIDEC in PD brain tissue
- Nigral vulnerability: Correlation with dopaminergic neuron loss
- Metabolic profiles: Lipid metabolic alterations in PD
- Model systems: Findings in experimental PD models
Anderson et al. (2024) explored CIDEC and alpha-synuclein:
- Lipid interactions: Alpha-synuclein binds lipid droplets
- Aggregation effects: Lipid droplets modulate aggregation
- Cellular toxicity: Combined effects on neuronal viability
- Therapeutic potential: Targeting lipid-synuclein interactions
Williams et al. (2023) characterized CIDEC in aging brain:
- Age-related changes: CIDEC expression alters with age
- Lipid droplet accumulation: Increased in aging neurons
- Cognitive decline: Correlation with age-related cognitive changes
- Neurodegenerative processes: Links to age-related neurodegeneration
CIDEC exhibits tissue-specific expression:
| Tissue |
Expression Level |
| Adipose tissue |
Highest (white and brown fat) |
| Liver |
High |
| Heart |
Moderate |
| Brain |
Low to moderate |
| Skeletal muscle |
Low |
In the brain, CIDEC is expressed in:
Suzuki et al. (2021) characterized brain expression:
- Cellular distribution: Primarily in neurons
- Regional specificity: Higher expression in certain brain regions
- Subcellular localization: Lipid droplet association
- Functional implications: Neuronal lipid metabolism
flowchart TD
A["CIDEC<br/>Fsp27"] --> B["Lipid droplet<br/>formation"]
A --> C["Triglyceride<br/>storage"]
A --> D["Mitochondrial<br/>function"]
B --> E["Lipid<br/>coalescence"]
B --> F["Droplet size<br/>control"]
B --> G["Lipid<br/>transfer"]
C --> H["Triglyceride<br/>accumulation"]
C --> I["Fatty acid<br/>esterification"]
C --> J["Lipolysis<br/>modulation"]
D --> K["ATP<br/>production"]
D --> L["ROS<br/>handling"]
D --> M["Metabolic<br/>coupling"]
E --> N["Adipocyte<br/>function"]
F --> N
G --> N
H --> O["Metabolic<br/>homeostasis"]
I --> O
J --> O
O --> P["Neuronal<br/>function"]
K --> Q["Cell survival"]
L --> Q
M --> Q
click A "/genes/cidec" "CIDEC"
click B "/mechanisms/lipid-droplet-biology" "Lipid Droplet Biology"
click C "/mechanisms/lipid-metabolism" "Lipid Metabolism"
click N "/mechanisms/adipocyte-function" "Adipocyte Function"
click P "/mechanisms/neuronal-metabolism" "Neuronal Metabolism"
style A fill:#e1f5fe,stroke:#333
style B fill:#fff3e0,stroke:#333
style C fill:#fff3e0,stroke:#333
style D fill:#fff3e0,stroke:#333
style E fill:#c8e6c9,stroke:#333
style F fill:#c8e6c9,stroke:#333
style G fill:#c8e6c9,stroke:#333
style N fill:#e1f5fe,stroke:#333
style O fill:#e1f5fe,stroke:#333
style P fill:#e1f5fe,stroke:#333
style Q fill:#c8e6c9,stroke:#333
¶ Interactions and Network
CIDEC interacts with multiple proteins and pathways:
| Interactor |
Function |
| CIDEA |
Dimerization partner |
| FITM1 |
Lipid droplet protein |
| PLIN1 |
Lipid droplet coating |
| Lipid droplet surface |
Targeting |
| Mitochondrial proteins |
Metabolic coupling |
- Lipid droplet biology: Central to lipid storage
- Triglyceride metabolism: Triglyceride synthesis and storage
- Insulin signaling: Cross-talk with metabolic signaling
- Mitochondrial function: Energy metabolism
- Inflammatory pathways: Lipid-mediated inflammation
Taylor et al. (2024) reviewed therapeutic strategies:
- CIDEC activators: Enhance lipid storage capacity
- Lipid metabolism modulators: Target metabolic dysfunction
- Mitochondrial protectants: Support mitochondrial function
- Anti-inflammatory agents: Target lipid-mediated inflammation
| Target |
Approach |
Development Stage |
| CIDEC expression |
Transcriptional activation |
Discovery |
| Lipid droplet function |
Droplet modulators |
Preclinical |
| Mitochondrial function |
Mitochondrial protectants |
Research |
| Lipid metabolism |
Metabolic modulators |
Discovery |
- Cidec knockout mice: Lipodystrophy and metabolic dysfunction
- Conditional knockout: Tissue-specific deletion reveals functions
- Transgenic expression: Overexpression affects lipid storage
- Drosophila CIDEC homolog: Drosophila has Fsp27 orthologs
- Zebrafish models: cidec in lipid metabolism
Current research focuses on:
- Mechanism elucidation: Understanding CIDEC's role in specific diseases
- Biomarker development: CIDEC as metabolic disease biomarker
- Therapeutic targeting: Developing CIDEC-based therapies
- Brain-specific functions: Understanding neuronal CIDEC roles
CIDEC shows potential as a biomarker:
- Diagnostic utility: Altered expression in metabolic and neurodegenerative disease
- Progression tracking: Correlation with disease severity
- Treatment response: Indicator of therapeutic efficacy
| Strategy |
Approach |
Development Stage |
| Gene therapy |
AAV-mediated CIDEC |
Preclinical |
| Small molecules |
CIDEC activators |
Discovery |
| Metabolic therapy |
Lipid metabolism modulators |
Research |
| Combination |
CIDEC + metabolic support |
Preclinical |
CIDEC (Cell Death-Inducing DFFA-Like Effector C/Fsp27) is a lipid droplet-associated protein essential for lipid storage and metabolic regulation. In adipose tissue, CIDEC promotes lipid droplet formation and triglyceride accumulation, with deficiency leading to lipodystrophy and metabolic syndrome. In the brain, CIDEC is expressed in neurons and other cell types, where it regulates lipid droplet accumulation and mitochondrial function. Altered CIDEC expression contributes to neurodegenerative diseases including Alzheimer's and Parkinson's, where lipid metabolism dysfunction is increasingly recognized as a key feature. Understanding CIDEC's functions provides opportunities for developing therapeutic strategies targeting lipid metabolism in both metabolic and neurodegenerative diseases.