Hepatic Elovl6 gene expression is regulated by the synergistic action of ChREBP and SREBP-1c

Bae, Jisuk; Oh, Ah-Reum; Lee, Hojae; Ahn, Yong-Ho; Cha, Ji-Young

doi:10.1016/j.bbrc.2016.08.061

Cited by 39 publications

(33 citation statements)

References 20 publications

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“…As a microsomal enzyme, Elovl6 is specially positioned in the endoplasmic reticulum, which played a crucial role in the elongation of palmitate (PA) or palmitoleate (POA) to stearate or cis-vaccenic acid [13,14]. Previous studies in mammals demonstrated that Elovl6 is also involved in inflammatory and metabolic diseases, such as high-fat-diet-induced inflammation and insulin resistance [3,6,15].…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization, Nutritional and Insulin Regulation of Elovl6 in Rainbow Trout (Oncorhynchus mykiss)

Pang

Zhao

et al. 2020

Biomolecules

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Elongation of very long-chain fatty acids protein 6 (Elovl6) is a crucial enzyme in the synthesis of endogenous fatty acids, which participates in the energy balance and metabolic diseases. The main objective of this study was to explore the molecular characterization of Elovl6 and the regulation of elovl6 expression in response to dietary fatty acids and insulin. In the present study, the ORF (open reading frame) of Elovl6 from rainbow trout was cloned and characterized, which showed a high identity (87%) with mammals and other teleost. The results of quantitative PCR showed that the transcriptional levels of elovl6 from rainbow trout that were fed diets containing soybean oil (enriched with 18:2n-6, linoleic acid (LA)) or linseed oil (enriched with 18:3n-3, α-linolenic acid (ALA)) were lower than those in the group that were fed diets containing fish oil (enriched with 20:5n-3, eicosapentaenoic acid (EPA) and 22:6n-3, docosahexaenoic acid (DHA)). Correspondingly, mRNA expression of elovl6 in hepatocytes treated with DHA was dramatically higher than that in LA and ALA groups. The transcriptional expression of elovl6 in hepatocytes treated with insulin was also significantly increased. Moreover, the dual luciferase assay showed the transcription factor CREB1 dramatically up-regulated the promoter activity of elovl6, while FOXO1 significantly down-regulated the elovl6 promoter activity in rainbow trout. The differences in transcriptional expression of crbe1 and foxo1 may contribute to the increase or decrease of elovl6 expression in rainbow trout in response to fatty acids or insulin. These findings revealed the molecular characterization of elovl6 and the regulation of elovl6 expression by CREB1 and FOXO1 in rainbow trout in response to dietary fatty acids or insulin.

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization, Nutritional and Insulin Regulation of Elovl6 in Rainbow Trout (Oncorhynchus mykiss)

Pang

Zhao

et al. 2020

Biomolecules

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“…Of note, in contrast to Srebp1c and its target genes, we did not find induction of either Scd-1 or Dgat2 at 6 h of refeeding among control mice. Previous studies demonstrating induction of these genes upon refeeding required high-carbohydrate or high-sucrose diets and/or more prolonged timepoints of refeeding (e.g., 12-24 h) (5,(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to inducing fatty acid synthesis genes, prolonged refeeding has been associated with induction of Scd-1, the enzyme catalyzing the conversion of saturated fatty acids to MUFAs, and diacylglycerol acyl-transferase 2 (Dgat2), controlling the final step in triglyceride synthesis (5,(24)(25)(26). In contrast to the pattern observed with fatty acid synthesis genes, we found no significant induction of hepatic Scd-1 and Dgat2 by 6 h of refeeding among Xbp1 fl/fl control mice (Fig.…”

Section: Hepatic Xbp1 Activates Hepatic Lipogenesis At a Posttranscrimentioning

confidence: 99%

The role of X-box binding protein 1 in the hepatic response to refeeding in mice

Olivares

Henkel

2019

Journal of Lipid Research

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Abbreviations: Acc, acyl-CoA carboxylase; CHOP, C/EBP homologous protein; Dgat2, diacylglycerol acyl-transferase 2; Dr5, death receptor 5; Edem, endoplasmic reticulum degradation enhancing mannoside; eIF2, eukaryotic initiation factor 2; ERo1, endoplasmic reticulum oxidase 1; IRE1, inositol requiring enzyme 1; Scd-1, stearoyl-CoA desaturase 1; Trb3, Tribbles-related protein 3; UPR, unfolded protein response; XBP1, X-box binding protein 1.

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“…Further works demonstrated that SREBF1 were the dominant transcription factors for mouse ELOVL6 [13, 14]. The findings on human compared with murine revealed another transcriptional regulation pattern that ChREBP and SREBF1 synergistically activated human ELOVL6 promoter [23]. ELOVL1, as a member of ELONGASE family, was regulated by mTOR through the activating the transcription factors SREBF1 and PPARγ in Cashmere goat [30].…”

Section: Discussionmentioning

confidence: 99%

“…Further ChIP assay showed that the proximal SRE-1 binding site on the promoter of ELOVL6 had higher affinity to SREBF1 than the distal one [22]. Meanwhile, a recent study suggested that human carbohydrate response element binding protein (ChREBP) and SREBF1 synergistically stimulated ELOVL6 promoter activity in HepG2 cell lines [23]. It has been demonstrated that a portion of transcriptional regulation which was activated by SREBPs requires cooperation with other DNA binding transcription factors such as SP1, NF-Y, and CREB as well as with coactivators [24].…”

Section: Introductionmentioning

confidence: 99%

Tissue expression profiles and transcriptional regulation of elongase of very long chain fatty acid 6 in bovine mammary epithelial cells

Chen

Liu

2017

PLoS ONE

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In mammals, very long chain fatty acids (VLCFAs) perform pleiotropic roles in a wide range of biological processes, such as cell membrane formation, cell signal transduction, and endocrine regulation. Beef and milk are abundant of palmitic acid which can be further elongated into stearic acid for synthesizing VLCFAs. Elongase of very long chain fatty acid 6 (ELOVL6) is a rate-limiting enzyme for converting palmitic acid to stearic acid. Consequently, investigating the tissue expression patterns and transcriptional regulation of bovine ELOVL6 can provide new insights into improving the composition of beneficial fats in cattle and expanding the knowledge of transcriptional regulation mechanism among domestic animals. In the current study, we found that bovine ELOVL6 expressed ubiquitously. Dual-luciferase reporter assay identified that the core promoter region (-130/-41 bp) was located in the second CpG island. In addition, the deletion mutation of binding sites demonstrated that sterol regulatory element binding transcription factor 1 (SREBF1) and specific protein 1 (SP1) both were able to stimulate bovine ELOVL6 promoter activity independently, while resulting the similar effect. To confirm these findings, further RNA interference assays were executed in bovine mammary epithelial cells (BMECs). In summary, these data suggest that bovine ELOVL6 expressed ubiquitously and is activated by SREBF1 and SP1, via two binding sites present in the ELOVL6 promoter region between -130 bp to -41bp.

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Hepatic Elovl6 gene expression is regulated by the synergistic action of ChREBP and SREBP-1c

Cited by 39 publications

References 20 publications

Molecular Characterization, Nutritional and Insulin Regulation of Elovl6 in Rainbow Trout (Oncorhynchus mykiss)

Molecular Characterization, Nutritional and Insulin Regulation of Elovl6 in Rainbow Trout (Oncorhynchus mykiss)

The role of X-box binding protein 1 in the hepatic response to refeeding in mice

Tissue expression profiles and transcriptional regulation of elongase of very long chain fatty acid 6 in bovine mammary epithelial cells

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