TY - JOUR
T1 - Dietary long-chain polyunsaturated fatty acids upregulate expression of FADS3 transcripts
AU - Reardon, Holly T.
AU - Hsieh, Andrea T.
AU - Jung Park, Woo
AU - Kothapalli, Kumar S.D.
AU - Anthony, Joshua C.
AU - Nathanielsz, Peter W.
AU - Thomas Brenna, J.
N1 - Funding Information:
H.R. was supported by a Ruth L. Kirchstein-NRSA predoctoral training fellowship in reproductive sciences and genomics (Grant Number T32HD052471 ) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or the NIH.
PY - 2013/1
Y1 - 2013/1
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 PPAR. γ antagonist GW9662 prevented FADS3 upregulation, while downregulation of FADS1 and FADS2 was unaffected. Thus, FADS3 AT were directly upregulated by LCPUFA by a PPAR. γ-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.
AB - 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 PPAR. γ antagonist GW9662 prevented FADS3 upregulation, while downregulation of FADS1 and FADS2 was unaffected. Thus, FADS3 AT were directly upregulated by LCPUFA by a PPAR. γ-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.
KW - Alternative splicing
KW - Arachidonic acid
KW - Docosahexaenoic acid
KW - FADS3
KW - Fatty acid desaturase
KW - Polyunsaturated fatty acids
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U2 - 10.1016/j.plefa.2012.02.003
DO - 10.1016/j.plefa.2012.02.003
M3 - Article
C2 - 22398025
AN - SCOPUS:84872010413
VL - 88
SP - 15
EP - 19
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
SN - 0952-3278
IS - 1
ER -