ADIG is indispensable for LD formation and adipose tissue function:
ADIG promotes LD growth by:
Stabilizing Seipin Complexes: ADIG selectively binds dodecameric seipin oligomers, enabling efficient triglyceride (TAG) sequestration .
Regulating LD Morphology: Overexpression in adipocytes enlarges LDs, while knockout leads to aberrant LD formation (e.g., smaller, fragmented LDs in brown adipose tissue) .
ADIG enhances cold-induced thermogenesis by:
Boosting Triglyceride Uptake: Overexpression in BAT increases TAG absorption from circulation, supporting heat production .
Maintaining Core Body Temperature: ADIG-deficient mice show impaired cold tolerance, linked to reduced BAT function .
ADIG expression is tightly regulated:
PPARγ Dependency: ADIG is transcriptionally activated by PPARγ, a master adipogenic regulator, during adipogenesis .
Genomic Associations: Variants near ADIG correlate with BMI-adjusted leptin levels, suggesting a role in obesity-related metabolic traits .
Inducible adipocyte-specific ADIG overexpression in mice yields:
Parameter | Outcome | Source |
---|---|---|
Fat Mass | ↑ BAT, sWAT, and eWAT weights | |
Lipid Metabolism | ↑ Triglyceride clearance; ↑ cholesterol in BAT | |
Thermogenesis | Attenuated core body temperature drop (cold exposure) |
ADIG knockout in adipocytes results in:
Parameter | Outcome | Source |
---|---|---|
BAT Morphology | Smaller LDs; impaired BAT expansion | |
Cold Tolerance | ↓ Core body temperature during cold stress | |
Triglyceride Uptake | Delayed clearance in BAT |
ADIG’s role in adipose tissue function is multifaceted:
Seipin Complex Stabilization: ADIG bridges seipin subunits, preventing aggregation and maintaining dodecameric symmetry .
Lipid Droplet Assembly: ADIG may act as part of the lipid droplet assembly complex (LDAC), facilitating TAG storage in high-demand tissues .
Cross-Tissue Metabolic Impact: Overexpression enhances systemic triglyceride metabolism, suggesting therapeutic potential for lipid-related disorders .
Human Relevance: Most studies use murine models; human ADIG’s role in obesity or metabolic diseases remains unexplored .
Therapeutic Potential: ADIG modulation could target lipid storage disorders or enhance cold-induced energy expenditure .
Structural Dynamics: The exact stoichiometry of ADIG-seipin interactions and its evolutionary conservation require further study .