Recombinant Human ELOVL3 (Elongation of Very Long Chain Fatty Acids Protein 3) is a synthetic version of the endogenous ELOVL3 enzyme, produced via recombinant DNA technology in E. coli systems . This protein belongs to the GNS1/SUR4 family and catalyzes the first and rate-limiting step in the elongation cycle of long-chain fatty acids (LCFAs), extending saturated/monounsaturated acyl-CoAs (C16–C18) into very long-chain fatty acids (VLCFAs, C20–C24) . Recombinant ELOVL3 is critical for studying lipid metabolism, cellular proliferation, and disease mechanisms, particularly in adipogenesis, liver regeneration, and retinal function .
Recombinant ELOVL3 is engineered with specific modifications for stability and functionality. Key features include:
Recombinant ELOVL3 replicates the endogenous enzyme’s role in VLCFA biosynthesis, influencing lipid homeostasis and cellular signaling.
ELOVL3 acts as a 3-ketoacyl-CoA synthase, condensing malonyl-CoA with acyl-CoA substrates to elongate fatty acid chains . Key substrates and products include:
ELOVL3 exhibits higher activity toward C18:0 acyl-CoAs, with lower efficiency for polyunsaturated substrates .
Recombinant ELOVL3 is utilized in diverse experimental contexts:
Zhx2 Regulation: Zhx2 transcriptionally activates Elovl3 in the liver. During regeneration, Elovl3 expression drops, correlating with reduced VLCFAs and impaired cell cycle progression .
Cell Cycle Impact: Forced Elovl3 expression stalls hepatoma cells in S-phase, reducing cyclin D/A/E mRNA levels .
PPARγ-ELOVL3 Cascade: Elovl3 expression peaks during adipocyte differentiation, driven by PPARγ. C18:1/C20:1 VLCFAs produced by ELOVL3 act as endogenous PPARγ agonists, enhancing triglyceride storage and adipogenic gene expression (e.g., aP2, SCD) .
siRNA Knockdown: Reduces triglycerides by 47% and suppresses lipogenic/lipolytic genes (e.g., ACC, FAS, ATGL) .
ELOVL3 vs. ELOVL4: While Elovl3 elongates saturated VLCFAs, Elovl4 synthesizes polyunsaturated VLC-PUFAs (e.g., C26–C34) critical for retinal membrane structure .
Metabolic Disorders: Dysregulated ELOVL3 may contribute to obesity/diabetes. VLCFAs enhance PPARγ signaling, suggesting therapeutic potential .
Liver Diseases: Suppressed Elovl3 in regenerating livers correlates with altered lipid profiles, implicating VLCFAs in hepatocyte proliferation .
Retinal Health: VLC-PUFAs, influenced by ELOVL3/4, are essential for photoreceptor integrity; disruptions may link to diseases like Stargardt’s .
Recombinant ELOVL3 requires careful handling to maintain activity:
ELOVL3 (Elongation of Very Long Chain Fatty Acids Protein 3) belongs to a family of genes (ELOVL 1-7) encoding enzymes that synthesize very long chain fatty acids (VLCFAs) . It catalyzes the first and rate-limiting reaction of the four reactions constituting the long-chain fatty acids elongation cycle . This endoplasmic reticulum-bound enzymatic process enables the addition of 2 carbon atoms to long- and very long-chain fatty acids per cycle . ELOVL3 specifically synthesizes C20-C24 saturated and monounsaturated fatty acids, exhibiting higher activity toward C18 acyl-CoAs, especially C18:0 acyl-CoAs .
The VLCFAs produced by ELOVL3 are commonly incorporated into ceramides or metabolized to lipid mediators that regulate cellular growth, differentiation, proliferation, and other physiological functions . These fatty acids serve as precursors of membrane lipids and bioactive lipid mediators involved in multiple biological processes .
ELOVL3 is expressed primarily in brown and white adipose tissue, skin sebaceous glands, and the liver . Its expression pattern varies developmentally, with extremely low expression in embryonic livers that increases postnatally . In mice, ELOVL3 exhibits sex-specific expression patterns, with male-biased expression becoming apparent between 4 and 8 weeks of age .
ELOVL3 expression is regulated by multiple transcription factors and signaling pathways:
ZHX2 (Zinc fingers and homeoboxes 2) acts as a transcriptional activator of hepatic ELOVL3 expression
Tumor suppressor p53 transcriptionally activates ELOVL3, connecting it to cell cycle regulation
Sex hormones significantly influence ELOVL3 expression, with androgens required for male-biased hepatic expression
Androgen receptor (AR) targets the ELOVL3 promoter and inhibits its transcriptional activity
Estrogen receptor signaling appears to maintain lower mRNA levels of ELOVL3 in female mice and cells
Microarray data from BALB/cJ mice (carrying a natural hypomorphic mutation in ZHX2) showed a positive correlation between ZHX2 and ELOVL3 expression levels . Studies using ChIP assays have confirmed that ZHX2 directly binds the ELOVL3 promoter and an upstream DHS to regulate transcription .
ELOVL3 appears to function as a negative regulator of cell proliferation. Evidence supporting this includes:
ELOVL3 mRNA levels are extremely low in embryonic livers, increase postnatally, and decrease dramatically during liver regeneration
Overexpression of ELOVL3 slows the in vitro growth of Huh7 cells and stalls HeLa cell cycle progression in S-phase
Forced ELOVL3 expression results in significant reductions in Cyclins D, A, and E, which are key regulators of cell cycle progression
ELOVL3 is transcriptionally activated by p53, a well-established tumor suppressor involved in cell cycle arrest
VLCFAs synthesized by ELOVL3 are often incorporated into ceramides, which are effective tumor suppressors that induce apoptosis and reduce proliferation through cell cycle arrest
ELOVL3 is also known by several alternative names:
CIG30 (Cold-inducible glycoprotein of 30 kDa)
3-keto acyl-CoA synthase ELOVL3
ELOVL fatty acid elongase 3
Very long chain 3-ketoacyl-CoA synthase 3
The human ELOVL3 protein functions as a condensing enzyme that exhibits activity toward saturated and unsaturated acyl-CoA substrates . Commercial antibodies against ELOVL3 are available for techniques including immunohistochemistry (IHC-P) and immunocytochemistry/immunofluorescence (ICC/IF) .