Gene regulation of mammalian desaturases

M. T. Nakamura, T. Y. Nara

Research output: Contribution to journalArticlepeer-review


Stearoyl-CoA desaturase (SCD) catalyses the synthesis of oleic acid (18: 1, n-9), which is mostly esterified into triacylglycerols (TAGs) as an energy reserve. Δ-6 Desaturase (D6D) and Δ-5 desaturase (D5D) are the key enzymes for the synthesis of highly unsaturated fatty acids (HUFAs), such as arachidonic acid (20:4, n-6) and docosahexaenoic acid (22:6, n-3), that are incorporated in phospholipids (PLs) and perform essential physiological functions. Despite these different physiological roles of SCD and D6D/D5D, these desaturases share common regulatory features, including dependence of expression on insulin, suppression by HUFAs, and induction by peroxisome proliferators (PPs). A key regulator of desaturase gene expression is sterol-regulatory element binding protein-1c (SREBP-1c), which mediates transcriptional activation of the SCD and D6D genes by insulin and inhibition by HUFAs. Because HUFAs are poorly incorporated into TAGs, the primary role of SREBP-1c in liver may be monitoring and regulating fatty acid composition in PLs rather than the regulation of TAG synthesis. The induction of desaturases by PPs is enigmatic because the major effect of PPs is induction of fatty acid oxidation enzymes by activating PP-activated receptor-α (PPARa). To our knowledge, no other gene that is induced by both SREBP-1 and PP has been identified. It is yet to be determined whether PPARa mediates the process directly. Available data suggest that the induction of desaturases by PPs may be a compensatory response to an increased demand for unsaturated fatty acids because PPs increase fatty acid degradation and induce proliferation of peroxisomes.

Original languageEnglish (US)
Pages (from-to)1076-1079
Number of pages4
JournalBiochemical Society transactions
Issue number6
StatePublished - Nov 2002


  • Peroxisome proliferator
  • Polyunsaturated fatty acids
  • Stearoyl-CoA desaturase
  • Sterol regulatory element binding protein
  • Δ-6 desaturase

ASJC Scopus subject areas

  • Biochemistry


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