ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3‐L1 and F442A cells

Kobayashi, Tsutomu; Zadravec, Damir; Jacobsson, Anders

doi:10.1016/j.febslet.2007.05.081

Cited by 42 publications

(29 citation statements)

References 46 publications

(59 reference statements)

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“…However, as previous data from our laboratory showed that overexpression of Elovl2 in adipocytes promoted TG formation and lipid accumulation accompanied by an induction of PPARγ target genes (28), we analyzed hepatic expression of PPARγ and some of its target genes.…”

Section: Resultsmentioning

confidence: 99%

Elovl2 ablation demonstrates that systemic DHA is endogenously produced and is essential for lipid homeostasis in mice

Pauter

Olsson

Asadi

et al. 2014

Journal of Lipid Research

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The potential role of endogenously synthesized PUFAs is a highly overlooked area. Elongation of very long-chain fatty acids (ELOVLs) in mammals is catalyzed by the ELOVL enzymes to which the PUFA elongase ELOVL2 belongs. To determine its in vivo function, we have investigated how ablation of ELOVL2, which is highly expressed in liver, affects hepatic lipid composition and function in mice. The Elovl2−/− mice displayed substantially decreased levels of 22:6(n-3), DHA, and 22:5(n-6), docosapentaenoic acid (DPA) n-6, and an accumulation of 22:5(n-3) and 22:4(n-6) in both liver and serum, showing that ELOVL2 primarily controls the elongation process of PUFAs with 22 carbons to produce 24-carbon precursors for DHA and DPAn-6 formation in vivo. The impaired PUFA levels positively influenced hepatic levels of the key lipogenic transcriptional regulator sterol-regulatory element binding protein 1c (SREBP-1c), as well as its downstream target genes. Surprisingly, the Elovl2−/− mice were resistant to hepatic steatosis and diet-induced weight gain, implying that hepatic DHA synthesis via ELOVL2, in addition to controlling de novo lipogenesis, also regulates lipid storage and fat mass expansion in an SREBP-1c-independent fashion. The changes in fatty acid metabolism were reversed by dietary supplementation with DHA.

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Section: Resultsmentioning

confidence: 99%

Elovl2 ablation demonstrates that systemic DHA is endogenously produced and is essential for lipid homeostasis in mice

Pauter

Olsson

Asadi

et al. 2014

Journal of Lipid Research

Self Cite

122

117

View full text Add to dashboard Cite

show abstract

“…The KCNJ15 gene encodes one of the potassium inward rectifying channels and is a type-2 diabetes risk gene and its up-regulation causes down regulation of glucose induced insulin release in mice and humans [33]. Similarly, the ELOVL2 gene (elongation of very long chain fatty acids 2) is located within 0.01 Mb upstream from SNP ASGA0030976 on SSC7 and is involved in enhancing the synthesis of triglycerides and deposition of lipid droplets in adipocytes [34]. The adipocytes usually produce leptin due to fat deposition [35].…”

Section: Resultsmentioning

confidence: 99%

Whole Genome Association Studies of Residual Feed Intake and Related Traits in the Pig

et al. 2013

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BackgroundResidual feed intake (RFI), a measure of feed efficiency, is the difference between observed feed intake and the expected feed requirement predicted from growth and maintenance. Pigs with low RFI have reduced feed costs without compromising their growth. Identification of genes or genetic markers associated with RFI will be useful for marker-assisted selection at an early age of animals with improved feed efficiency.Methodology/Principal findingsWhole genome association studies (WGAS) for RFI, average daily feed intake (ADFI), average daily gain (ADG), back fat (BF) and loin muscle area (LMA) were performed on 1,400 pigs from the divergently selected ISU-RFI lines, using the Illumina PorcineSNP60 BeadChip. Various statistical methods were applied to find SNPs and genomic regions associated with the traits, including a Bayesian approach using GenSel software, and frequentist approaches such as allele frequency differences between lines, single SNP and haplotype analyses using PLINK software. Single SNP and haplotype analyses showed no significant associations (except for LMA) after genomic control and FDR. Bayesian analyses found at least 2 associations for each trait at a false positive probability of 0.5. At generation 8, the RFI selection lines mainly differed in allele frequencies for SNPs near (<0.05 Mb) genes that regulate insulin release and leptin functions. The Bayesian approach identified associations of genomic regions containing insulin release genes (e.g., GLP1R, CDKAL, SGMS1) with RFI and ADFI, of regions with energy homeostasis (e.g., MC4R, PGM1, GPR81) and muscle growth related genes (e.g., TGFB1) with ADG, and of fat metabolism genes (e.g., ACOXL, AEBP1) with BF. Specifically, a very highly significantly associated QTL for LMA on SSC7 with skeletal myogenesis genes (e.g., KLHL31) was identified for subsequent fine mapping.Conclusions/significanceImportant genomic regions associated with RFI related traits were identified for future validation studies prior to their incorporation in marker-assisted selection programs.

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“…Finally, rs1150561 near ELOVL2 was associated with poorer L response. The product of this gene catalyzes the elongation of EPA to DHA (Kobayashi et al., 2007). Although our study suggests that ELOVL2 and FADS1 polymorphisms may also relate to L and MPOD response respectively, the mechanism of this relationship is uncertain, but it is probably connected to processes governing lipid composition in serum.…”

Section: Discussionmentioning

confidence: 99%

Candidate gene study of macular response to supplemental lutein and zeaxanthin

Yonova-Doing

Hysi

Venturini

et al. 2013

Experimental Eye Research

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Supplementation with carotenoids is proposed to protect against age-related macular degeneration. There is, however, considerable variability in retinal macular pigment response, which may be due to underlying genetic variation. The purpose of this study was to determine whether genetic factors, which have been previously associated with cross-sectional macular pigment levels in the retina or serum lutein, also influence response to supplementation.To this end we conducted an association study in 310 subjects from the TwinsUK cohort between variants in 8 candidate genes and serum lutein and retinal macular pigment optical density (MPOD) levels before and after supplementation. Four variants were associated with MPOD response to supplementation (p < 0.05): rs11057841 (SCARB1), rs4926339 (RPE65), rs1929841 (ABCA1) and rs174534 (FADS1). We also confirmed previous associations between rs6564851 near BMCO1 (p < 0.001) and rs11057841 within SCARB1 (p = 0.01) and baseline measures of serum lutein; while the latter was also associated with MPOD response, none of the BMCO1 variants were. Finally, there was evidence for association between variants near RPE65 and ELOVL2 and changes in lutein concentration after supplementation.This study is the first to show association between genetic variants and response to carotenoids supplementation. Our findings suggest an important link between MP response and the biological processes of carotenoids transport and fatty acid metabolism.

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ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3‐L1 and F442A cells

Cited by 42 publications

References 46 publications

Elovl2 ablation demonstrates that systemic DHA is endogenously produced and is essential for lipid homeostasis in mice

Elovl2 ablation demonstrates that systemic DHA is endogenously produced and is essential for lipid homeostasis in mice

Whole Genome Association Studies of Residual Feed Intake and Related Traits in the Pig

Candidate gene study of macular response to supplemental lutein and zeaxanthin

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