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Long‐chain acyl‐CoA synthetase 3 (ACSL3) mediates transcriptional control of hepatic lipogenesis
Author(s) -
Bu So Young,
Mashek Mara T,
Mashek Douglas G
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.522.9
Subject(s) - gene knockdown , lipogenesis , biology , lipid metabolism , steatosis , gene isoform , reporter gene , microbiology and biotechnology , biochemistry , gene expression , endocrinology , gene
Long‐chain acyl‐CoA synthetases (ACSL) and fatty acid transport proteins (FATP) activate fatty acids (FAs) to acyl‐CoAs and each isoform of ACSL and FATP has different tissue distribution patterns, intracellular locations and substrate preferences. Since FAs and acyl‐CoAs affect the regulation of various transcription factors that govern hepatic energy metabolism, we hypothesize that distinct pools of intracellular FAs and acyl‐CoAs governed by ACSL or FATP isoforms differentially regulate hepatic gene expression. To test this hypothesis, we knocked down each ACSL and FATP isoform in rat primary hepatocyte cultures using siRNA and analyzed reporter gene activity of transcription factors (PPAR‐gamma, SREBP and LXR‐alpha). Of the different ACSL and FATP isoforms, knockdown of ACSL3 significantly decreased PPAR‐gamma reporter gene activity. ACSL3 knockdown also down regulated the expression of lipogenic genes. These findings were further supported by metabolic labeling studies showing that ACSL3 knockdown resulted in decreased [C14]acetate incorporation into lipids. In summary, these results indicate that activation and channeling of FAs by ACSL3 mediates lipogenic pathways in the liver. The mechanism by which ACSL3 regulates these transcriptional factors governing lipogenesis needs to be further investigated.