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Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3 transcripts.

Abstract

The fatty acid desaturase (FADS) gene family at 11q12-13.1 includes FADS1 and FADS2, both known to mediate biosynthesis of omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA). FADS3 is a putative desaturase due to its sequence similarity with FADS1 and FADS2, but its function is unknown. We have previously described 7 FADS3 alternative transcripts (AT) and 1 FADS2 AT conserved across multiple species. This study examined the effect of dietary LCPUFA levels on liver FADS gene expression in vivo and in vitro, evaluated by qRT-PCR. Fourteen baboon neonates were randomized to three diet groups for their first 12 weeks of life, C: Control, no LCPUFA, L: 0.33% docosahexaenoic acid (DHA)/0.67% arachidonic acid (ARA) (w/w); and L3: 1.00% DHA/0.67% ARA (w/w). Liver FADS1 and both FADS2 transcripts were downregulated by at least 50% in the L3 group compared to controls. In contrast, FADS3 AT were upregulated (L3 > C), with four transcripts significantly upregulated by 40% or more. However, there was no evidence for a shift in liver fatty acids to coincide with increased FADS3 expression. Significant upregulation of FADS3 AT was also observed in human liver-derived HepG2 cells after DHA or ARA treatment. The PPARγ antagonist GW9662 prevented FADS3 upregulation, while downregulation of FADS1 and FADS2 was unaffected. Thus, FADS3 AT were directly upregulated by LCPUFA by a PPARγ-dependent mechanism unrelated to regulation of other desaturases. This opposing pattern and mechanism of regulation suggests a dissimilar function for FADS3 AT compared to other FADS gene products.

Authors+Show Affiliations

Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22398025

Citation

Reardon, Holly T., et al. "Dietary Long-chain Polyunsaturated Fatty Acids Upregulate Expression of FADS3 Transcripts." Prostaglandins, Leukotrienes, and Essential Fatty Acids, vol. 88, no. 1, 2013, pp. 15-9.
Reardon HT, Hsieh AT, Park WJ, et al. Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3 transcripts. Prostaglandins Leukot Essent Fatty Acids. 2013;88(1):15-9.
Reardon, H. T., Hsieh, A. T., Park, W. J., Kothapalli, K. S., Anthony, J. C., Nathanielsz, P. W., & Brenna, J. T. (2013). Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3 transcripts. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 88(1), 15-9. https://doi.org/10.1016/j.plefa.2012.02.003
Reardon HT, et al. Dietary Long-chain Polyunsaturated Fatty Acids Upregulate Expression of FADS3 Transcripts. Prostaglandins Leukot Essent Fatty Acids. 2013;88(1):15-9. PubMed PMID: 22398025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3 transcripts. AU - Reardon,Holly T, AU - Hsieh,Andrea T, AU - Park,Woo Jung, AU - Kothapalli,Kumar S D, AU - Anthony,Joshua C, AU - Nathanielsz,Peter W, AU - Brenna,J Thomas, Y1 - 2012/03/06/ PY - 2011/12/20/received PY - 2012/02/10/accepted PY - 2012/3/9/entrez PY - 2012/3/9/pubmed PY - 2013/7/5/medline SP - 15 EP - 9 JF - Prostaglandins, leukotrienes, and essential fatty acids JO - Prostaglandins Leukot. Essent. Fatty Acids VL - 88 IS - 1 N2 - The fatty acid desaturase (FADS) gene family at 11q12-13.1 includes FADS1 and FADS2, both known to mediate biosynthesis of omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFA). FADS3 is a putative desaturase due to its sequence similarity with FADS1 and FADS2, but its function is unknown. We have previously described 7 FADS3 alternative transcripts (AT) and 1 FADS2 AT conserved across multiple species. This study examined the effect of dietary LCPUFA levels on liver FADS gene expression in vivo and in vitro, evaluated by qRT-PCR. Fourteen baboon neonates were randomized to three diet groups for their first 12 weeks of life, C: Control, no LCPUFA, L: 0.33% docosahexaenoic acid (DHA)/0.67% arachidonic acid (ARA) (w/w); and L3: 1.00% DHA/0.67% ARA (w/w). Liver FADS1 and both FADS2 transcripts were downregulated by at least 50% in the L3 group compared to controls. In contrast, FADS3 AT were upregulated (L3 > C), with four transcripts significantly upregulated by 40% or more. However, there was no evidence for a shift in liver fatty acids to coincide with increased FADS3 expression. Significant upregulation of FADS3 AT was also observed in human liver-derived HepG2 cells after DHA or ARA treatment. The PPARγ antagonist GW9662 prevented FADS3 upregulation, while downregulation of FADS1 and FADS2 was unaffected. Thus, FADS3 AT were directly upregulated by LCPUFA by a PPARγ-dependent mechanism unrelated to regulation of other desaturases. This opposing pattern and mechanism of regulation suggests a dissimilar function for FADS3 AT compared to other FADS gene products. SN - 1532-2823 UR - https://www.unboundmedicine.com/medline/citation/22398025/Dietary_long_chain_polyunsaturated_fatty_acids_upregulate_expression_of_FADS3_transcripts_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0952-3278(12)00009-9 DB - PRIME DP - Unbound Medicine ER -